Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA GO_REF:0000033	ACCEPT	Summary: ELT-2 is a well-characterized GATA transcription factor that binds specifically to WGATAR sequences in promoters of target genes. This sequence-specific DNA binding has been demonstrated in multiple studies including direct visualization of ELT-2 binding in living embryos (PMID:10518545) and in vitro binding assays (PMID:15733671, PMID:15734735). Reason: This IBA annotation is well-supported by the phylogenetic inference and is consistent with extensive experimental evidence from C. elegans showing ELT-2 binds specifically to cis-regulatory regions containing GATA motifs (PMID:10518545, PMID:15733671). Supporting Evidence: PMID:10518545 We previously have shown, by means of ectopic expression studies, that elt-2 regulates its own promoter. To test whether this autoregulation is direct, we fused green fluorescent protein (GFP) close to the C terminus of elt-2 in a construct that contains the full elt-2 promoter and the full elt-2 zinc finger DNA binding domain PMID:15733671 The gut-specific GATA factor ELT-2 binds to this site in vitro and removal of ELT-2 from the embryo destroys expression of the pho-1 reporter. file:worm/elt-2/elt-2-deep-research-falcon.md model: Edison Scientific Literature
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IBA GO_REF:0000033	ACCEPT	Summary: ELT-2 is a bona fide transcription factor that activates transcription of intestinal genes. Multiple studies demonstrate it binds DNA and activates RNA polymerase II-dependent transcription (PMID:9659934, PMID:14573471, PMID:26963674). Reason: Core molecular function of ELT-2 as a transcription factor is well-established through multiple experimental studies showing it activates transcription of target genes. Supporting Evidence: PMID:14573471 Whereas ELT-2 protein is a strong transcriptional activator in yeast PMID:9659934 When elt-2 is expressed ectopically using a transgenic heat-shock construct, the endogenous ges-1 gene is now expressed in most if not all cells of the embryo
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Nuclear localization of ELT-2 is well-documented. ELT-2::GFP fusion protein localizes to discrete foci within nuclei of gut cells (PMID:10518545, PMID:16968778). Reason: Consistent with experimental evidence from multiple publications demonstrating nuclear localization of ELT-2 protein in intestinal cells. Supporting Evidence: PMID:10518545 the majority of these embryonic gut nuclei show two discrete intense foci of fluorescence
GO:0045944 positive regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	ACCEPT	Summary: ELT-2 is a transcriptional activator that positively regulates transcription of many intestinal genes including ges-1, pho-1, spl-1, vit-2, and genes involved in immune responses (PMID:9659934, PMID:15733671, PMID:15734735, PMID:26963674). Reason: Core function of ELT-2. Multiple studies demonstrate ELT-2 activates transcription of target genes in the intestine. Supporting Evidence: PMID:9659934 When elt-2 is expressed ectopically using a transgenic heat-shock construct, the endogenous ges-1 gene is now expressed in most if not all cells of the embryo PMID:15733671 gut expression is critically dependent on a single WGATAR site. The gut-specific GATA factor ELT-2 binds to this site in vitro and removal of ELT-2 from the embryo destroys expression of the pho-1 reporter. Thus, all our results indicate that pho-1 is a direct downstream target of ELT-2.
GO:0000122 negative regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: While ELT-2 is primarily a transcriptional activator, the IBA annotation suggests some GATA factors in the family can also repress transcription. The PMID:26016853 study found a cluster of genes upregulated upon elt-2 knockdown, suggesting possible repressive function for some genes. Reason: The primary function of ELT-2 is as a transcriptional activator. While there is evidence from microarray studies (PMID:26016853) that some genes are upregulated upon elt-2 knockdown, this appears to be a minor or indirect function. The IBA annotation derives from related GATA factors that may have more prominent repressive roles. Supporting Evidence: PMID:26016853 a cluster of 43 genes showing elevated expression following elt-2 knock-down, suggesting repression by the transcription factor ('elt-2-repressed')
GO:0045165 cell fate commitment	IBA GO_REF:0000033	ACCEPT	Summary: ELT-2 plays a role in intestinal cell fate specification, working with ELT-7 to control endoderm differentiation. The specification-differentiation transition in the endoderm involves ELT-2 function (PMID:9659934). Reason: ELT-2 is essential for intestinal development and terminal differentiation, and works synergistically with ELT-7 in endoderm specification. This is consistent with the IBA annotation. Supporting Evidence: PMID:9659934 Homozygous elt-2 null mutants die at the L1 larval stage with an apparent malformation or degeneration of gut cells
GO:0000976 transcription cis-regulatory region binding	IEA GO_REF:0000117	ACCEPT	Summary: This IEA annotation is consistent with the more specific IBA and IDA annotations for RNA polymerase II cis-regulatory region binding. Reason: Accurate but less specific than GO:0000978. ELT-2 does bind cis-regulatory regions as demonstrated experimentally.
GO:0003677 DNA binding	IEA GO_REF:0000043	ACCEPT	Summary: General DNA binding annotation. ELT-2 contains a GATA-type zinc finger DNA-binding domain and binds DNA specifically. Reason: Accurate but very general. More specific DNA-binding annotations (GO:0000977, GO:0000978) provide better functional information.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000002	ACCEPT	Summary: ELT-2 is clearly a DNA-binding transcription factor. This annotation from InterPro is accurate. Reason: Fundamental function of ELT-2 supported by extensive experimental evidence.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Nuclear localization is well-established for ELT-2. Reason: Duplicate of other nucleus annotations. Accurate but redundant with experimentally-supported annotations.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	ACCEPT	Summary: ELT-2 regulates DNA-templated transcription as a transcription factor. Reason: Core function consistent with ELT-2's role as a transcription factor.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000002	ACCEPT	Summary: ELT-2 regulates transcription of intestinal genes. Reason: Accurate. ELT-2 is a transcriptional regulator controlling expression of intestinal genes.
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000002	ACCEPT	Summary: ELT-2 regulates RNA polymerase II-dependent transcription. Reason: Accurate. ELT-2 is a transcription factor that regulates Pol II transcription.
GO:0008270 zinc ion binding	IEA GO_REF:0000120	ACCEPT	Summary: ELT-2 contains a GATA-type zinc finger domain that coordinates zinc for DNA binding. Reason: ELT-2 has a conserved GATA-type zinc finger domain (amino acids 237-261 per UniProt) that requires zinc for function.
GO:0009888 tissue development	IEA GO_REF:0000117	MODIFY	Summary: ELT-2 is essential for intestinal (tissue) development. Reason: While accurate, this term is too general. ELT-2 specifically regulates endoderm/intestinal development. Proposed replacements: endoderm development
GO:0030154 cell differentiation	IEA GO_REF:0000043	ACCEPT	Summary: ELT-2 is required for terminal differentiation of intestinal cells. Reason: ELT-2 controls intestinal cell differentiation, though a more specific term could be used.
GO:0043565 sequence-specific DNA binding	IEA GO_REF:0000002	ACCEPT	Summary: ELT-2 binds specifically to WGATAR sequences. Reason: Well-established that ELT-2 binds DNA in a sequence-specific manner (PMID:10518545, PMID:15733671).
GO:0046872 metal ion binding	IEA GO_REF:0000043	ACCEPT	Summary: ELT-2 binds zinc through its GATA zinc finger domain. Reason: Accurate but general. The more specific GO:0008270 (zinc ion binding) is also annotated.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:16968778 A conserved role for a GATA transcription factor in regulati...	ACCEPT	Summary: PMID:16968778 demonstrates ELT-2 is required for transcriptional activation of immune response genes in the intestine during P. aeruginosa infection. RNAi knockdown of elt-2 prevents induction of immune genes. Reason: Strong experimental evidence from mutant phenotype analysis showing ELT-2 positively regulates transcription of immune response genes. Supporting Evidence: PMID:16968778 Gene expression and functional RNAi-based analyses identified the tissue-specific GATA transcription factor ELT-2 as a major regulator of an early intestinal protective response to infection with the human bacterial pathogen Pseudomonas aeruginosa.
GO:0005634 nucleus	IDA PMID:20126308 Genetic and physiological activation of osmosensitive gene e...	ACCEPT	Summary: Nuclear localization of ELT-2 is well established from multiple studies using ELT-2::GFP fusion proteins that show discrete fluorescent foci within intestinal cell nuclei. Reason: Direct experimental evidence of nuclear localization from multiple studies. The PMID:20126308 reference is primarily about osmotic stress responses, but nuclear localization of ELT-2 is well supported by PMID:10518545. Supporting Evidence: PMID:10518545 the majority of these embryonic gut nuclei show two discrete intense foci of fluorescence PMID:20126308 Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:20126308 Genetic and physiological activation of osmosensitive gene e...	ACCEPT	Summary: PMID:20126308 shows ELT-2 is required for transcriptional activation of osmotic stress response genes in the intestine. Reason: Experimental evidence showing ELT-2 activates transcription of osmosensitive genes through GATA binding sites. Supporting Evidence: PMID:20126308 RNAi against one GATA factor, elt-2, attenuated osmotically induced GFP expression in the intestine without substantially affecting hypodermal GFP expression
GO:0008340 determination of adult lifespan	IMP PMID:24834345 Transcriptional regulation of Caenorhabditis elegans FOXO/DA...	KEEP AS NON CORE	Summary: PMID:24834345 demonstrates ELT-2 regulates lifespan through transcriptional control of daf-16 isoforms in the intestine. Reason: While ELT-2 does influence lifespan through regulation of daf-16, this is a downstream consequence of its core transcriptional regulatory function in the intestine, not its primary biological role. Supporting Evidence: PMID:24834345 we identify elt-2 (GATA transcription factor) and swsn-1 (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene expression. ELT-2 and another GATA factor, ELT-4, promote longevity via both DAF-16a and DAF-16d/f
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:24834345 Transcriptional regulation of Caenorhabditis elegans FOXO/DA...	ACCEPT	Summary: PMID:24834345 shows ELT-2 activates transcription of daf-16 isoforms. Reason: Direct experimental evidence of ELT-2 positively regulating transcription of daf-16 genes. Supporting Evidence: PMID:24834345 ELT-2 and another GATA factor, ELT-4, are required for the expression of both daf-16a and daf-16d/f
GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA PMID:26963674 A 44 bp intestine-specific hermaphrodite-specific enhancer f...	ACCEPT	Summary: PMID:26963674 demonstrates direct binding of ELT-2 to the vit-2 enhancer element. Reason: Direct experimental evidence of ELT-2 binding to specific cis-regulatory sequence. Supporting Evidence: PMID:26963674 an activator site that we show is the direct target of the intestinal GATA factor ELT-2
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IMP PMID:26963674 A 44 bp intestine-specific hermaphrodite-specific enhancer f...	ACCEPT	Summary: PMID:26963674 provides evidence ELT-2 functions as a transcription factor regulating the vit-2 enhancer. Reason: Experimental evidence of transcription factor activity at vit-2 enhancer. Supporting Evidence: PMID:26963674 A 44-bp region from the vit-2 gene promoter is able largely to reconstitute this tissue-, stage- and sex-specific-expression...an activator site that we show is the direct target of the intestinal GATA factor ELT-2
GO:0005634 nucleus	IDA PMID:26963674 A 44 bp intestine-specific hermaphrodite-specific enhancer f...	ACCEPT	Summary: Nuclear localization confirmed by imaging studies. Reason: Consistent with other experimental evidence of nuclear localization. Supporting Evidence: PMID:26963674 2016 Mar 7. A 44 bp intestine-specific hermaphrodite-specific enhancer from the C.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:26963674 A 44 bp intestine-specific hermaphrodite-specific enhancer f...	ACCEPT	Summary: ELT-2 activates transcription of vit-2 through direct enhancer binding. Reason: Strong experimental evidence of ELT-2 activating vit-2 transcription. Supporting Evidence: PMID:26963674 an activator site that we show is the direct target of the intestinal GATA factor ELT-2
GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific	IDA PMID:14573471 The evolutionary duplication and probable demise of an endod...	ACCEPT	Summary: PMID:14573471 characterizes ELT-2 as a transcriptional activator using yeast assays and demonstrates sequence-specific DNA binding. Reason: Direct experimental evidence of transcription factor activity. Supporting Evidence: PMID:14573471 Whereas ELT-2 protein is a strong transcriptional activator in yeast
GO:0004857 enzyme inhibitor activity	IDA PMID:29361115 The GATA transcription factor ELT-2 modulates both the expre...	KEEP AS NON CORE	Summary: PMID:29361115 shows ELT-2 physically interacts with PRMT-1 and inhibits its methyltransferase activity in a dose-dependent manner. This is an unusual non-transcriptional function of ELT-2. Reason: This is a non-canonical function of ELT-2 distinct from its primary role as a transcription factor. The study demonstrates direct protein-protein interaction between ELT-2 and PRMT-1 leading to inhibition of PRMT-1 methyltransferase activity, but this appears to be a specialized regulatory mechanism rather than a core function. Supporting Evidence: PMID:29361115 GST pull-down and co-immunoprecipitation assays demonstrate the interaction between ELT-2 and PRMT-1. Furthermore, we find that ELT-2 interferes with PRMT-1-induced arginine methylation in a dose-dependent manner.
GO:0010468 regulation of gene expression	IMP PMID:26016853 The Developmental Intestinal Regulator ELT-2 Controls p38-De...	ACCEPT	Summary: PMID:26016853 demonstrates ELT-2 regulates expression of intestinal genes including immune response genes and digestive enzymes. Reason: Comprehensive experimental evidence from microarray analysis showing ELT-2 regulates hundreds of genes in the adult intestine. Supporting Evidence: PMID:26016853 Microarray analysis identified two ELT-2-regulated gene subsets: one, enriched for hydrolytic enzymes, pointed at regulation of constitutive digestive functions as a dominant role of adult elt-2; the second was enriched for immune genes that are induced in response to Pseudomonas aeruginosa infection.
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:26016853 The Developmental Intestinal Regulator ELT-2 Controls p38-De...	ACCEPT	Summary: PMID:26016853 shows ELT-2 is required for immune responses to P. aeruginosa, a Gram-negative bacterium. Reason: Strong experimental evidence that ELT-2 controls p38-dependent immune gene induction in response to P. aeruginosa infection. Supporting Evidence: PMID:26016853 we show that elt-2 controls p38-dependent gene induction, cooperating with two p38-activated transcription factors, ATF-7 and SKN-1. This demonstrates a mechanism through which the constitutively nuclear elt-2 can impact induced responses, and play a dominant role in C. elegans immunity.
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA PMID:10518545 Direct visualization of the elt-2 gut-specific GATA factor b...	ACCEPT	Summary: PMID:10518545 directly visualizes ELT-2 binding to its own promoter in living embryos using ELT-2::GFP fusion protein. Reason: Elegant direct experimental demonstration of ELT-2 binding to regulatory DNA sequences in vivo. Supporting Evidence: PMID:10518545 We interpret these fluorescent foci as the result of ELT-2::GFP binding directly to its own promoter within nuclei of the developing gut lineage. Numerous control experiments, both genetic and biochemical, all support this conclusion and support the specificity of the binding.
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA PMID:15733671 Transcriptional control and patterning of the pho-1 gene, an...	ACCEPT	Summary: PMID:15733671 demonstrates ELT-2 binds to WGATAR site in pho-1 promoter. Reason: In vitro binding assays and functional analysis confirm ELT-2 binding to pho-1 regulatory region. Supporting Evidence: PMID:15733671 Transgenic analysis of the pho-1 promoter shows that gut expression is critically dependent on a single WGATAR site. The gut-specific GATA factor ELT-2 binds to this site in vitro
GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA PMID:15734735 Regulation of sphingosine-1-phosphate lyase gene expression ...	ACCEPT	Summary: PMID:15734735 demonstrates ELT-2 binds to GATA motif in spl-1 (sphingosine-1-phosphate lyase) promoter. Reason: In vitro binding and functional analysis confirm ELT-2 regulation of spl-1 through GATA binding site. Supporting Evidence: PMID:15734735 ELT-2 interacted with the GATA factor-binding motif in vitro and was also capable of driving expression of a Caenorhabditis elegans lyase promoter-beta-galactosidase reporter in a heterologous yeast system.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:15734735 Regulation of sphingosine-1-phosphate lyase gene expression ...	ACCEPT	Summary: PMID:15734735 shows ELT-2 activates sphingosine-1-phosphate lyase gene expression. Reason: Experimental evidence of ELT-2 activating spl-1 transcription through direct binding to GATA motif. Supporting Evidence: PMID:15734735 These studies demonstrate that ELT-2 regulates sphingosine-1-phosphate lyase expression in vivo.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:15734735 Regulation of sphingosine-1-phosphate lyase gene expression ...	ACCEPT	Summary: Mutant analysis supports ELT-2's role in activating spl-1 transcription. Reason: RNAi knockdown demonstrates ELT-2 is required for spl-1 expression. Supporting Evidence: PMID:15734735 Knockdown of the gut-specific GATA transcription factor ELT-2 by RNA interference similarly led to loss of reporter expression.
GO:0002119 nematode larval development	IMP PMID:21868609 Cell architecture: surrounding muscle cells shape gland cell...	ACCEPT	Summary: PMID:21868609 is primarily about pharyngeal gland morphology but notes that elt-2 RNAi causes highly penetrant L1 lethality, confirming ELT-2's essential role in larval development. Reason: The paper confirms that elt-2 RNAi causes L1 lethality, consistent with ELT-2's essential role in larval development established by PMID:9659934. Supporting Evidence: PMID:21868609 elt-2(RNAi) gives a highly penetrant (∼100%) L1 lethality by feeding
GO:0045087 innate immune response	IMP PMID:16968778 A conserved role for a GATA transcription factor in regulati...	ACCEPT	Summary: PMID:16968778 demonstrates ELT-2 is a major regulator of intestinal innate immune responses to P. aeruginosa infection. Reason: Strong experimental evidence that ELT-2 is required for innate immune responses in the intestine. Supporting Evidence: PMID:16968778 Gene expression and functional RNAi-based analyses identified the tissue-specific GATA transcription factor ELT-2 as a major regulator of an early intestinal protective response to infection with the human bacterial pathogen Pseudomonas aeruginosa.
GO:0005634 nucleus	IDA PMID:16968778 A conserved role for a GATA transcription factor in regulati...	ACCEPT	Summary: Nuclear localization confirmed in this study. Reason: Consistent with multiple other studies showing nuclear localization. Supporting Evidence: PMID:16968778 A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:16968778 A conserved role for a GATA transcription factor in regulati...	ACCEPT	Summary: PMID:16968778 shows ELT-2 is required for defense against P. aeruginosa. Reason: Key study establishing ELT-2's role in immune defense against Gram-negative bacteria. Supporting Evidence: PMID:16968778 In the adult worm, ELT-2 is required specifically for infection responses and survival on pathogen but makes no significant contribution to gene expression associated with intestinal maintenance or to resistance to cadmium, heat, and oxidative stress.
GO:0050829 defense response to Gram-negative bacterium	HEP PMID:16968778 A conserved role for a GATA transcription factor in regulati...	ACCEPT	Summary: High-throughput expression data from PMID:16968778 supports ELT-2's role in defense response. Reason: Microarray expression profiling provides additional evidence for ELT-2's role in immune gene regulation. Supporting Evidence: PMID:16968778 A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.
GO:0003700 DNA-binding transcription factor activity	IMP PMID:14573471 The evolutionary duplication and probable demise of an endod...	ACCEPT	Summary: PMID:14573471 demonstrates ELT-2 is a transcriptional activator. Reason: Experimental evidence from yeast assays showing ELT-2 has transcription factor activity. Supporting Evidence: PMID:14573471 Whereas ELT-2 protein is a strong transcriptional activator in yeast
GO:0007492 endoderm development	IMP PMID:14573471 The evolutionary duplication and probable demise of an endod...	ACCEPT	Summary: PMID:14573471 discusses ELT-2's role in endoderm/intestinal development. Reason: Core developmental function of ELT-2 in endoderm differentiation. Supporting Evidence: PMID:14573471 The elt-2 gene is expressed only in the intestine and is essential for normal intestinal development.
GO:0045944 positive regulation of transcription by RNA polymerase II	IDA PMID:14573471 The evolutionary duplication and probable demise of an endod...	ACCEPT	Summary: Direct demonstration of ELT-2 transcriptional activation activity. Reason: Yeast one-hybrid assays directly demonstrate ELT-2 activates transcription. Supporting Evidence: PMID:14573471 Whereas ELT-2 protein is a strong transcriptional activator in yeast, ELT-4 protein has no such activity under similar conditions
GO:0002119 nematode larval development	IMP PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caen...	ACCEPT	Summary: PMID:9659934 shows elt-2 null mutants die at L1 stage, demonstrating essential role in larval development. Reason: elt-2 is essential for larval survival and development - null mutants arrest at L1 stage. Supporting Evidence: PMID:9659934 Homozygous elt-2 null mutants die at the L1 larval stage with an apparent malformation or degeneration of gut cells.
GO:0003690 double-stranded DNA binding	IDA PMID:14573471 The evolutionary duplication and probable demise of an endod...	ACCEPT	Summary: PMID:14573471 demonstrates ELT-2 binds to double-stranded DNA containing GATA sequences. Reason: In vitro binding experiments confirm ELT-2 binds dsDNA. Supporting Evidence: PMID:14573471 In vitro binding experiments could not detect specific binding of ELT-4 protein to candidate binding sites (double-stranded oligonucleotides containing single or multiple WGATAR sequences); ELT-4 protein neither enhanced nor inhibited the strong sequence-specific binding of the ELT-2 protein.
GO:0005634 nucleus	IDA PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caen...	ACCEPT	Summary: Original study demonstrating ELT-2 nuclear localization. Reason: Key early evidence of nuclear localization of ELT-2. Supporting Evidence: PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine.
GO:0007492 endoderm development	IMP PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caen...	ACCEPT	Summary: PMID:9659934 establishes ELT-2 as essential for intestinal/endoderm development. Reason: Foundational study establishing ELT-2's essential role in endoderm development. Supporting Evidence: PMID:9659934 Homozygous elt-2 null mutants die at the L1 larval stage with an apparent malformation or degeneration of gut cells.
GO:0007586 digestion	IMP PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caen...	ACCEPT	Summary: PMID:9659934 shows elt-2 null mutants have defective intestinal function. PMID:26016853 demonstrates ELT-2 regulates expression of hydrolytic enzymes involved in constitutive digestive functions in the adult intestine. Reason: ELT-2 regulates expression of digestive enzymes in the intestine and loss of elt-2 leads to digestive defects. Microarray analysis confirms ELT-2 controls hydrolytic enzyme expression. Supporting Evidence: PMID:26016853 one, enriched for hydrolytic enzymes, pointed at regulation of constitutive digestive functions as a dominant role of adult elt-2 PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine.
GO:0030856 regulation of epithelial cell differentiation	IMP PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caen...	ACCEPT	Summary: ELT-2 regulates differentiation of intestinal epithelial cells. Reason: ELT-2 controls terminal differentiation of intestinal epithelial cells. Supporting Evidence: PMID:9659934 loss of elt-2 function has major consequences for later gut morphogenesis and function
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:9659934 The GATA-factor elt-2 is essential for formation of the Caen...	ACCEPT	Summary: PMID:9659934 shows ectopic ELT-2 expression activates ges-1 transcription. Reason: Ectopic expression experiments demonstrate ELT-2 activates transcription of intestinal genes. Supporting Evidence: PMID:9659934 When elt-2 is expressed ectopically using a transgenic heat-shock construct, the endogenous ges-1 gene is now expressed in most if not all cells of the embryo

Core Functions

ELT-2 is a GATA-type transcription factor that binds to WGATAR sequences and activates transcription of intestinal genes. Demonstrated through in vitro binding, yeast activation assays, and in vivo visualization (PMID:10518545, PMID:14573471, PMID:15733671, PMID:15734735).

Molecular Function:

DNA-binding transcription factor activity, RNA polymerase II-specific

Directly Involved In:

endoderm development innate immune response digestion

Cellular Locations:

nucleus

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

ELT-2 belongs to the GATA transcription factor family with conserved DNA-binding and transcriptional regulatory functions

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:9659934

The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine.

ELT-2 is essential for intestinal development

"The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine."
elt-2 null mutants die at L1 larval stage with malformed gut cells

"The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine."
elt-2 is expressed gut-specifically from 2E cell stage through adulthood

"The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine."
Ectopic elt-2 expression causes ectopic ges-1 expression

"The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine."
ELT-2 likely autoregulates its own promoter

"The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine."

PMID:10518545

Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo.

ELT-2::GFP binds to elt-2 promoter in discrete nuclear foci in living embryos

"Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo."
ELT-2 directly autoregulates its own promoter

"Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo."
Demonstrates sequence-specific DNA binding in vivo

"Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo."

PMID:14573471

The evolutionary duplication and probable demise of an endodermal GATA factor in Caenorhabditis elegans.

ELT-2 is a strong transcriptional activator in yeast assays

"The evolutionary duplication and probable demise of an endodermal GATA factor in Caenorhabditis elegans."
ELT-2 binds specifically to WGATAR sequences in vitro

"The evolutionary duplication and probable demise of an endodermal GATA factor in Caenorhabditis elegans."
ELT-4 is a duplicated but apparently non-functional paralog

"The evolutionary duplication and probable demise of an endodermal GATA factor in Caenorhabditis elegans."

PMID:15733671

Transcriptional control and patterning of the pho-1 gene, an essential acid phosphatase expressed in the C. elegans intestine.

pho-1 is a direct target of ELT-2

"Transcriptional control and patterning of the pho-1 gene, an essential acid phosphatase expressed in the C. elegans intestine."
ELT-2 binds to WGATAR site in pho-1 promoter in vitro

"Transcriptional control and patterning of the pho-1 gene, an essential acid phosphatase expressed in the C. elegans intestine."
Loss of ELT-2 destroys pho-1 reporter expression

"Transcriptional control and patterning of the pho-1 gene, an essential acid phosphatase expressed in the C. elegans intestine."

PMID:15734735

Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors.

ELT-2 regulates sphingosine-1-phosphate lyase (spl-1) expression

"Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors."
ELT-2 binds GATA motif in spl-1 promoter

"Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors."
ELT-2 can activate spl-1 promoter in yeast system

"Regulation of sphingosine-1-phosphate lyase gene expression by members of the GATA family of transcription factors."

PMID:16968778

A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.

ELT-2 is major regulator of intestinal immune responses to P. aeruginosa

"A conserved role for a GATA transcription factor in regulating epithelial innate immune responses."
Required for infection responses and survival on pathogen

"A conserved role for a GATA transcription factor in regulating epithelial innate immune responses."
Function is conserved - human GATA6 has similar protective role

"A conserved role for a GATA transcription factor in regulating epithelial innate immune responses."
ELT-2 does not contribute to resistance to cadmium, heat, or oxidative stress

"A conserved role for a GATA transcription factor in regulating epithelial innate immune responses."

PMID:20126308

Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.

ELT-2 mediates osmosensitive gene expression in intestine

"Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans."
Works with ELT-3 (hypodermal) for organismal osmotic stress resistance

"Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans."
GATA binding sites required for osmosensitive gene activation

"Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans."

PMID:24834345

Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan.

ELT-2 regulates daf-16d/f isoform expression in intestine

"Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan."
Required for daf-16 expression and lifespan extension

"Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan."
ELT-2 and ELT-4 promote longevity via DAF-16a and DAF-16d/f

"Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan."

PMID:26016853

The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans.

ELT-2 controls p38-dependent immune gene induction

"The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans."
Cooperates with ATF-7 and SKN-1 downstream of p38

"The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans."
Regulates constitutive digestive enzyme expression in adults

"The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans."
Essential for both basal and induced immune gene expression

"The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent Immune Responses in Adult C. elegans."

PMID:26963674

A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16.

ELT-2 directly binds and activates 44bp vit-2 enhancer

"A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway."
Works with MAB-3, FKH-9, and DAF-16 to regulate vit-2

"A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway."

PMID:29361115

The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans.

ELT-2 regulates prmt-1 expression transcriptionally

"The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans."
ELT-2 physically interacts with PRMT-1 protein

"The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans."
ELT-2 inhibits PRMT-1 methyltransferase activity through protein interaction

"The GATA transcription factor ELT-2 modulates both the expression and methyltransferase activity of PRMT-1 in Caenorhabditis elegans."

PMID:21868609

Cell architecture: surrounding muscle cells shape gland cell morphology in the Caenorhabditis elegans pharynx.

Used elt-2::GFP as marker for intestinal cells

"Cell architecture: surrounding muscle cells shape gland cell morphology in the Caenorhabditis elegans pharynx."
Not a direct study of elt-2 function

"Cell architecture: surrounding muscle cells shape gland cell morphology in the Caenorhabditis elegans pharynx."

file:worm/elt-2/elt-2-deep-research-falcon.md

Deep research report on elt-2

📚 Additional Documentation

Deep Research Falcon

(elt-2-deep-research-falcon.md)

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organism_full: Caenorhabditis elegans.
protein_family: Not specified in UniProt
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q10655
Protein Description: RecName: Full=Transcription factor elt-2 {ECO:0000305}; AltName: Full=GATA-type domain-containing protein elt-2 {ECO:0000305};
Gene Information: Name=elt-2 {ECO:0000312|WormBase:C33D3.1}; ORFNames=C33D3.1 {ECO:0000312|WormBase:C33D3.1};
Organism (full): Caenorhabditis elegans.
Protein Family: Not specified in UniProt
Key Domains: Transcription_factor_GATA. (IPR039355); Znf_GATA. (IPR000679); Znf_NHR/GATA. (IPR013088); GATA (PF00320)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "elt-2" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'elt-2' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene elt-2 (gene ID: elt-2, UniProt: Q10655) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: Q10655
Protein Description: RecName: Full=Transcription factor elt-2 {ECO:0000305}; AltName: Full=GATA-type domain-containing protein elt-2 {ECO:0000305};
Gene Information: Name=elt-2 {ECO:0000312|WormBase:C33D3.1}; ORFNames=C33D3.1 {ECO:0000312|WormBase:C33D3.1};
Organism (full): Caenorhabditis elegans.
Protein Family: Not specified in UniProt
Key Domains: Transcription_factor_GATA. (IPR039355); Znf_GATA. (IPR000679); Znf_NHR/GATA. (IPR013088); GATA (PF00320)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "elt-2" matches the protein description above
Verify the organism is correct: Caenorhabditis elegans.
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene elt-2 (gene ID: elt-2, UniProt: Q10655) in worm.

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Plan and approach
- Verify identity and domain features; ensure organism specificity and symbol disambiguation.
- Compile primary and recent literature on ELT-2 function, localization, regulatory mechanisms, and pathway crosstalk; prioritize 2023–2024 studies but integrate foundational work where needed.
- Extract quantitative data (gene set enrichments, motif statistics, DEGs, epistasis, survival, lifespan, ChIP–qPCR).
- Synthesize into a comprehensive, cited research report with URLs and publication dates.

Research report: C. elegans elt-2 (UniProt Q10655) – functional annotation

1) Identity, key concepts, and definitions
- Gene/protein identity and domains: elt-2 encodes a C. elegans intestine-restricted GATA-family transcription factor with a canonical GATA-type zinc-finger DNA-binding domain. It is constitutively nuclear in intestinal cells and functions primarily as a transcriptional regulator rather than an enzyme or transporter. Foundational and mechanistic studies consistently define ELT-2 as the terminal differentiation GATA factor for the intestine and a master regulator of adult intestinal gene expression and immunity (PLOS Genetics, 2015-05-28, https://doi.org/10.1371/journal.pgen.1005265; Worm, 2015-10-23, https://doi.org/10.1080/21624054.2015.1118607) (block2015thedevelopmentalintestinal pages 1-2, block2015gatatranscriptionfactors pages 2-3).
- Developmental context and definition: In the endoderm gene regulatory network (GRN), maternal and early zygotic inputs establish an interlocked GATA cascade culminating in ELT-2 (with ELT-7) to specify and differentiate the gut. Reviews and syntheses place ELT-2 downstream of SKN-1 → MED-1/2 → END-1/3, acting with partial redundancy with ELT-7 for terminal intestinal gene expression across embryo to adult (Dissertation, 2022, pages dated 2022; https://scholarworks.unavailable) (williams2022investigationoftranscriptional pages 79-82, williams2022investigationoftranscriptional pages 72-75).

2) Mechanisms, localization, and direct/indirect targets
- Subcellular localization: ELT-2 is constitutively nuclear in intestinal cells through larval and adult stages, consistent with a role in both basal and inducible transcriptional programs (PLOS Genetics, 2015-05-28; Worm, 2015-10-23) (block2015thedevelopmentalintestinal pages 1-2, block2015gatatranscriptionfactors pages 2-3).
- Direct DNA recognition and promoter landscape: ELT-2 targets are significantly enriched for proximal promoter GATA motifs. For the “elt-2-induced” adult set, 72% of genes harbor TGATAA motifs in the proximal promoter versus ~42% genome-wide, with strong hypergeometric significance; microarray profiling during infection identified 426 elt-2–responsive transcripts (PLOS Genetics, 2015-05-28) (block2015thedevelopmentalintestinal pages 4-5).
- Target classes and regulatory polarity: Adult ELT-2 regulates two dominant gene classes: (i) digestive/hydrolytic enzymes (proteases, lipases, lysozymes) supporting intestinal function; and (ii) innate immune effectors (e.g., C-type lectins, lysozymes), many of which are induced upon pathogen exposure. ELT-2 control is selective: several structural intestinal genes are not altered by adult elt-2 knockdown (act-5, ifb-2, etc.), indicating a refined regulatory scope (PLOS Genetics, 2015-05-28; Worm, 2015-10-23; URLs above) (block2015thedevelopmentalintestinal pages 5-7, block2015thedevelopmentalintestinal pages 4-5, block2015gatatranscriptionfactors pages 2-3).

3) Pathway integration in adult intestine immunity and stress
- PMK-1/p38 → ATF-7 and SKN-1 cooperation: In adults, ELT-2 acts as a tissue-specific master regulator of p38/PMK-1–dependent innate immune induction. Pathogen exposure activates PMK-1, which phosphorylates ATF-7 to convert it from repressor to activator; ATF-7 then cooperates with ELT-2 to induce immune genes. SKN-1 contributes to a subset, activated via PMK-1 and/or ROS. Genetic epistasis and qRT–PCR/survival assays support that elt-2 is required for effective expression of many ATF-7–dependent targets, and for subsets of SKN-1 targets (e.g., F55G11.2, C32H11.12). Overlap analyses show 38% and 33% of sek-1/pmk-1 targets intersect with elt-2 sets (PLOS Genetics, 2015-05-28; Worm, 2015-10-23) (block2015thedevelopmentalintestinal pages 5-7, block2015thedevelopmentalintestinal pages 9-11, block2015thedevelopmentalintestinal pages 11-13, block2015gatatranscriptionfactors pages 2-3).
- Neuro-immune modulation (2024): Loss of the neuronal GPCR NPR-15 activates immunity while suppressing avoidance. Transcriptomics and functional assays show that enhanced pathogen resistance in npr-15 mutants requires ELT-2 and HLH-30/TFEB; elt-2 RNAi abrogates the resistance phenotype. Enrichment analyses place ELT-2 alongside PMK-1 and DAF-16 programs, indicating coordinated regulation across intestinal and neuronal axes via ASJ sensory neurons (eLife, 2024-03-08, https://doi.org/10.7554/eLife.90051) (otarigho2024neuronalnpr15modulates pages 4-6).
- Proteostasis/lysosome surveillance and healthspan (recent advance): Silencing vha-6 (intestinal V-ATPase) elicits a lysosomal surveillance response (LySR) that extends lifespan by ~60%. ELT-2 is required for LySR activation and longevity: elt-2 RNAi attenuates LySR reporter induction; ELT-2 ChIP–qPCR shows robust binding to promoters of lysosomal proteases (cpr-5, cpr-8, ctsa-1, asp-10) upon LySR activation (P < 0.0001). Transcriptomics revealed thousands of DEGs including innate immune and lysosome-related genes, with ELT-2 central to executing the program (Nature Cell Biology, 2025-06-17, https://doi.org/10.1038/s41556-025-01693-y) (li2025alysosomalsurveillance pages 5-6).

4) Developmental roles and gene network logic
- Cascade and redundancy: ELT-2 and ELT-7 are partially redundant terminal differentiation GATA factors in the endoderm GRN. ELT-2’s influence spans embryo to adult, with dynamic regulatory impacts and both activation and repression within intestinal networks; negative autoregulatory features and feedforward logic help ensure robust fate-locking and functional maturation (Dissertation, 2022) (williams2022investigationoftranscriptional pages 79-82, williams2022investigationoftranscriptional pages 72-75).

5) Current applications, real-world implementations, and data
- Infection and immunity assays: Adult-specific elt-2 knockdown reduces resistance to diverse enteric pathogens and suppresses induction of ELT-2 target immune genes; epistasis with p38 components (nsy-1/sek-1/pmk-1) delineates dependency and cooperation (PLOS Genetics, 2015-05-28; Worm, 2015-10-23; URLs above) (block2015thedevelopmentalintestinal pages 5-7, block2015thedevelopmentalintestinal pages 11-13, block2015gatatranscriptionfactors pages 2-3).
- Neuro-immune axis manipulation: npr-15 mutants exhibit ELT-2- and HLH-30-dependent enhanced resistance; genetic perturbation of elt-2 reverts this phenotype, providing a framework to probe gut–brain immune regulation and candidate therapeutic axes in host–pathogen studies (eLife, 2024-03-08; URL above) (otarigho2024neuronalnpr15modulates pages 4-6).
- Proteostasis/aging paradigms: Intestinal V-ATPase perturbation (vha-6 RNAi) engages an ELT-2–dependent LySR, improving proteostasis and extending lifespan, positioning ELT-2 as a lever for healthspan interventions in nematode models (Nature Cell Biology, 2025-06-17; URL above) (li2025alysosomalsurveillance pages 5-6).

6) Quantitative statistics and data highlights
- Promoter motif enrichment: 72% of elt-2-induced genes carry proximal GATA motifs vs 42% genome-wide; hypergeometric enrichment highly significant (PLOS Genetics, 2015-05-28) (block2015thedevelopmentalintestinal pages 4-5).
- Gene overlaps: 38% (sek-1) and 33% (pmk-1) targets overlap with elt-2 gene sets, supporting pathway integration (PLOS Genetics, 2015-05-28) (block2015thedevelopmentalintestinal pages 5-7).
- Differential expression breadth: 426 transcripts differentially expressed upon adult elt-2 RNAi during infection challenge; immune GO terms significantly enriched (e.g., innate immunity p = 1.5 × 10−15) (PLOS Genetics, 2015-05-28) (block2015thedevelopmentalintestinal pages 4-5, block2015thedevelopmentalintestinal pages 5-7).
- LySR and longevity: Lifespan extension of ~60% with vha-6 RNAi; ELT-2 ChIP–qPCR enrichment at lysosomal protease promoters upon LySR activation (P < 0.0001), and broad DEGs (thousands) in lysosome/immune categories (Nature Cell Biology, 2025-06-17) (li2025alysosomalsurveillance pages 5-6).
- Neuro-immune functional requirement: Enhanced resistance of npr-15 mutants is reversed by elt-2 RNAi; RNA-seq enrichments highlight ELT-2, HLH-30, PMK-1, DAF-16 signatures; qRT–PCR validated multiple ELT-2 target effectors (eLife, 2024-03-08) (otarigho2024neuronalnpr15modulates pages 4-6).

7) Expert opinions and synthesis
- Tissue-specific master regulator: ELT-2 is best understood as a constitutive, intestine-restricted GATA TF that scaffolds inducible programs through cooperation with stress and immune TFs (ATF-7, SKN-1), conferring specificity and robustness to adult intestinal defenses while maintaining digestive capacity (Worm, 2015-10-23; PLOS Genetics, 2015-05-28) (block2015gatatranscriptionfactors pages 2-3, block2015thedevelopmentalintestinal pages 1-2, block2015thedevelopmentalintestinal pages 9-11).
- Integration with broader stress and longevity programs: Recent findings place ELT-2 as a critical executor of lysosomal/proteostasis responses that extend healthspan, and as a node receiving neuronal regulation to tune intestinal immunity, indicating a broader physiological role beyond classical gut differentiation (eLife, 2024-03-08; Nature Cell Biology, 2025-06-17) (otarigho2024neuronalnpr15modulates pages 4-6, li2025alysosomalsurveillance pages 5-6).

8) Gaps and limitations in the present evidence set
- While multiple studies implicate ELT-2 alongside DAF-16 and HLH-30 programs, direct biochemical mapping of ELT-2’s interactions with these factors in 2023–2024 literature is limited in the current corpus. Similarly, although ELT-2 is often used as a benchmark in microbiome and TGF-β/DBL-1 studies, direct 2023–2024 mechanistic dissection linking ELT-2 to microbiome composition or DBL-1 signaling is not available in the evidence assembled here; these connections should be interpreted cautiously and warrant further targeted review (context grounded by 2015–2024 sources above) (block2015thedevelopmentalintestinal pages 5-7, block2015gatatranscriptionfactors pages 2-3, otarigho2024neuronalnpr15modulates pages 4-6).

Conclusions
ELT-2 is the canonical intestine-specific GATA transcription factor in C. elegans, constitutively nuclear and essential for terminal intestinal gene expression. In adults, ELT-2 selectively regulates digestive/hydrolytic functions and orchestrates p38/PMK-1–dependent innate immune programs by cooperating with ATF-7 and SKN-1, with substantial promoter GATA motif enrichment and pathway target overlap. Recent work expands ELT-2’s significance to neuronally modulated immunity via NPR-15/ASJ and to lysosomal-proteostasis programs that extend lifespan, underscoring ELT-2 as a central hub integrating immune, stress, and longevity pathways in the intestinal epithelium (citations and URLs above) (block2015thedevelopmentalintestinal pages 5-7, block2015thedevelopmentalintestinal pages 9-11, block2015gatatranscriptionfactors pages 2-3, otarigho2024neuronalnpr15modulates pages 4-6, li2025alysosomalsurveillance pages 5-6).

References

(block2015thedevelopmentalintestinal pages 1-2): Dena H. S. Block, Kwame Twumasi-Boateng, Hae Sung Kang, Jolie A. Carlisle, Alexandru Hanganu, Ty Yu-Jen Lai, and Michael Shapira. The developmental intestinal regulator elt-2 controls p38-dependent immune responses in adult c. elegans. PLOS Genetics, 11:e1005265, May 2015. URL: https://doi.org/10.1371/journal.pgen.1005265, doi:10.1371/journal.pgen.1005265. This article has 65 citations and is from a domain leading peer-reviewed journal.
(block2015gatatranscriptionfactors pages 2-3): Dena Hs Block and Michael Shapira. Gata transcription factors as tissue-specific master regulators for induced responses. Worm, 4:e1118607, Oct 2015. URL: https://doi.org/10.1080/21624054.2015.1118607, doi:10.1080/21624054.2015.1118607. This article has 32 citations.
(williams2022investigationoftranscriptional pages 79-82): RTP Williams. Investigation of transcriptional dynamics in the caenorhabditis elegans intestine gene regulatory network. Unknown journal, 2022.
(williams2022investigationoftranscriptional pages 72-75): RTP Williams. Investigation of transcriptional dynamics in the caenorhabditis elegans intestine gene regulatory network. Unknown journal, 2022.
(block2015thedevelopmentalintestinal pages 4-5): Dena H. S. Block, Kwame Twumasi-Boateng, Hae Sung Kang, Jolie A. Carlisle, Alexandru Hanganu, Ty Yu-Jen Lai, and Michael Shapira. The developmental intestinal regulator elt-2 controls p38-dependent immune responses in adult c. elegans. PLOS Genetics, 11:e1005265, May 2015. URL: https://doi.org/10.1371/journal.pgen.1005265, doi:10.1371/journal.pgen.1005265. This article has 65 citations and is from a domain leading peer-reviewed journal.
(block2015thedevelopmentalintestinal pages 5-7): Dena H. S. Block, Kwame Twumasi-Boateng, Hae Sung Kang, Jolie A. Carlisle, Alexandru Hanganu, Ty Yu-Jen Lai, and Michael Shapira. The developmental intestinal regulator elt-2 controls p38-dependent immune responses in adult c. elegans. PLOS Genetics, 11:e1005265, May 2015. URL: https://doi.org/10.1371/journal.pgen.1005265, doi:10.1371/journal.pgen.1005265. This article has 65 citations and is from a domain leading peer-reviewed journal.
(block2015thedevelopmentalintestinal pages 9-11): Dena H. S. Block, Kwame Twumasi-Boateng, Hae Sung Kang, Jolie A. Carlisle, Alexandru Hanganu, Ty Yu-Jen Lai, and Michael Shapira. The developmental intestinal regulator elt-2 controls p38-dependent immune responses in adult c. elegans. PLOS Genetics, 11:e1005265, May 2015. URL: https://doi.org/10.1371/journal.pgen.1005265, doi:10.1371/journal.pgen.1005265. This article has 65 citations and is from a domain leading peer-reviewed journal.
(block2015thedevelopmentalintestinal pages 11-13): Dena H. S. Block, Kwame Twumasi-Boateng, Hae Sung Kang, Jolie A. Carlisle, Alexandru Hanganu, Ty Yu-Jen Lai, and Michael Shapira. The developmental intestinal regulator elt-2 controls p38-dependent immune responses in adult c. elegans. PLOS Genetics, 11:e1005265, May 2015. URL: https://doi.org/10.1371/journal.pgen.1005265, doi:10.1371/journal.pgen.1005265. This article has 65 citations and is from a domain leading peer-reviewed journal.
(otarigho2024neuronalnpr15modulates pages 4-6): Benson Otarigho, Anna Frances Butts, and Alejandro Aballay. Neuronal npr-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis in c. elegans. eLife, Mar 2024. URL: https://doi.org/10.7554/elife.90051, doi:10.7554/elife.90051. This article has 5 citations and is from a domain leading peer-reviewed journal.
(li2025alysosomalsurveillance pages 5-6): Terytty Yang Li, Arwen W. Gao, Rendan Yang, Yu Sun, Yuxuan Lei, Xiaoxu Li, Lin Chen, Yasmine J. Liu, Rachel N. Arey, Kimberly Morales, Raya B. Liu, Wenzheng Wang, Ang Zhou, Tong-jin Zhao, Weisha Li, Amélia Lalou, Qi Wang, Tanes Lima, Riekelt H. Houtkooper, and Johan Auwerx. A lysosomal surveillance response to stress extends healthspan. Nature Cell Biology, 27:1083-1097, Jun 2025. URL: https://doi.org/10.1038/s41556-025-01693-y, doi:10.1038/s41556-025-01693-y. This article has 5 citations and is from a highest quality peer-reviewed journal.

Citations

block2015thedevelopmentalintestinal pages 4-5
li2025alysosomalsurveillance pages 5-6
block2015thedevelopmentalintestinal pages 5-7
block2015thedevelopmentalintestinal pages 1-2
block2015gatatranscriptionfactors pages 2-3
williams2022investigationoftranscriptional pages 79-82
williams2022investigationoftranscriptional pages 72-75
block2015thedevelopmentalintestinal pages 9-11
block2015thedevelopmentalintestinal pages 11-13
https://doi.org/10.1371/journal.pgen.1005265;
https://doi.org/10.1080/21624054.2015.1118607
https://scholarworks.unavailable
https://doi.org/10.7554/eLife.90051
https://doi.org/10.1038/s41556-025-01693-y
https://doi.org/10.1371/journal.pgen.1005265,
https://doi.org/10.1080/21624054.2015.1118607,
https://doi.org/10.7554/elife.90051,
https://doi.org/10.1038/s41556-025-01693-y,

📄 View Raw YAML

id: Q10655
gene_symbol: elt-2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: ELT-2 is a GATA-type transcription factor that serves as the master
  regulator of intestinal gene expression in C. elegans. It contains a single 
  GATA-type zinc finger DNA-binding domain and binds to the consensus sequence 
  5'-[AT]GATA[AG]-3'. ELT-2 is expressed exclusively in the intestine from 
  embryogenesis through adulthood, beginning at the 2E cell stage. It is 
  essential for intestinal development and function - null mutants die at the L1
  larval stage with malformed or degenerated gut cells. ELT-2 is the predominant
  transcription factor controlling both constitutive intestinal gene expression 
  (including digestive enzymes) and induced innate immune responses to bacterial
  pathogens. It works in parallel with the p38 MAPK/PMK-1 pathway to regulate 
  immune gene induction, cooperating with transcription factors ATF-7 and SKN-1.
  Additionally, ELT-2 regulates lifespan through transcriptional control of 
  daf-16 isoforms in the intestine.
existing_annotations:
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ELT-2 is a well-characterized GATA transcription factor that binds 
      specifically to WGATAR sequences in promoters of target genes. This 
      sequence-specific DNA binding has been demonstrated in multiple studies 
      including direct visualization of ELT-2 binding in living embryos 
      (PMID:10518545) and in vitro binding assays (PMID:15733671, 
      PMID:15734735).
    action: ACCEPT
    reason: This IBA annotation is well-supported by the phylogenetic inference 
      and is consistent with extensive experimental evidence from C. elegans 
      showing ELT-2 binds specifically to cis-regulatory regions containing GATA
      motifs (PMID:10518545, PMID:15733671).
    supported_by:
    - reference_id: PMID:10518545
      supporting_text: We previously have shown, by means of ectopic expression 
        studies, that elt-2 regulates its own promoter. To test whether this 
        autoregulation is direct, we fused green fluorescent protein (GFP) close
        to the C terminus of elt-2 in a construct that contains the full elt-2 
        promoter and the full elt-2 zinc finger DNA binding domain
    - reference_id: PMID:15733671
      supporting_text: The gut-specific GATA factor ELT-2 binds to this site in 
        vitro and removal of ELT-2 from the embryo destroys expression of the 
        pho-1 reporter.
    - reference_id: file:worm/elt-2/elt-2-deep-research-falcon.md
      supporting_text: 'model: Edison Scientific Literature'
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ELT-2 is a bona fide transcription factor that activates 
      transcription of intestinal genes. Multiple studies demonstrate it binds 
      DNA and activates RNA polymerase II-dependent transcription (PMID:9659934,
      PMID:14573471, PMID:26963674).
    action: ACCEPT
    reason: Core molecular function of ELT-2 as a transcription factor is 
      well-established through multiple experimental studies showing it 
      activates transcription of target genes.
    supported_by:
    - reference_id: PMID:14573471
      supporting_text: Whereas ELT-2 protein is a strong transcriptional 
        activator in yeast
    - reference_id: PMID:9659934
      supporting_text: When elt-2 is expressed ectopically using a transgenic 
        heat-shock construct, the endogenous ges-1 gene is now expressed in most
        if not all cells of the embryo
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Nuclear localization of ELT-2 is well-documented. ELT-2::GFP fusion
      protein localizes to discrete foci within nuclei of gut cells 
      (PMID:10518545, PMID:16968778).
    action: ACCEPT
    reason: Consistent with experimental evidence from multiple publications 
      demonstrating nuclear localization of ELT-2 protein in intestinal cells.
    supported_by:
    - reference_id: PMID:10518545
      supporting_text: the majority of these embryonic gut nuclei show two 
        discrete intense foci of fluorescence
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ELT-2 is a transcriptional activator that positively regulates 
      transcription of many intestinal genes including ges-1, pho-1, spl-1, 
      vit-2, and genes involved in immune responses (PMID:9659934, 
      PMID:15733671, PMID:15734735, PMID:26963674).
    action: ACCEPT
    reason: Core function of ELT-2. Multiple studies demonstrate ELT-2 activates
      transcription of target genes in the intestine.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: When elt-2 is expressed ectopically using a transgenic 
        heat-shock construct, the endogenous ges-1 gene is now expressed in most
        if not all cells of the embryo
    - reference_id: PMID:15733671
      supporting_text: gut expression is critically dependent on a single WGATAR
        site. The gut-specific GATA factor ELT-2 binds to this site in vitro and
        removal of ELT-2 from the embryo destroys expression of the pho-1 
        reporter. Thus, all our results indicate that pho-1 is a direct 
        downstream target of ELT-2.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: While ELT-2 is primarily a transcriptional activator, the IBA 
      annotation suggests some GATA factors in the family can also repress 
      transcription. The PMID:26016853 study found a cluster of genes 
      upregulated upon elt-2 knockdown, suggesting possible repressive function 
      for some genes.
    action: KEEP_AS_NON_CORE
    reason: The primary function of ELT-2 is as a transcriptional activator. 
      While there is evidence from microarray studies (PMID:26016853) that some 
      genes are upregulated upon elt-2 knockdown, this appears to be a minor or 
      indirect function. The IBA annotation derives from related GATA factors 
      that may have more prominent repressive roles.
    supported_by:
    - reference_id: PMID:26016853
      supporting_text: a cluster of 43 genes showing elevated expression 
        following elt-2 knock-down, suggesting repression by the transcription 
        factor ('elt-2-repressed')
- term:
    id: GO:0045165
    label: cell fate commitment
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: ELT-2 plays a role in intestinal cell fate specification, working 
      with ELT-7 to control endoderm differentiation. The 
      specification-differentiation transition in the endoderm involves ELT-2 
      function (PMID:9659934).
    action: ACCEPT
    reason: ELT-2 is essential for intestinal development and terminal 
      differentiation, and works synergistically with ELT-7 in endoderm 
      specification. This is consistent with the IBA annotation.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: Homozygous elt-2 null mutants die at the L1 larval stage 
        with an apparent malformation or degeneration of gut cells
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: This IEA annotation is consistent with the more specific IBA and 
      IDA annotations for RNA polymerase II cis-regulatory region binding.
    action: ACCEPT
    reason: Accurate but less specific than GO:0000978. ELT-2 does bind 
      cis-regulatory regions as demonstrated experimentally.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: General DNA binding annotation. ELT-2 contains a GATA-type zinc 
      finger DNA-binding domain and binds DNA specifically.
    action: ACCEPT
    reason: Accurate but very general. More specific DNA-binding annotations 
      (GO:0000977, GO:0000978) provide better functional information.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ELT-2 is clearly a DNA-binding transcription factor. This 
      annotation from InterPro is accurate.
    action: ACCEPT
    reason: Fundamental function of ELT-2 supported by extensive experimental 
      evidence.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Nuclear localization is well-established for ELT-2.
    action: ACCEPT
    reason: Duplicate of other nucleus annotations. Accurate but redundant with 
      experimentally-supported annotations.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ELT-2 regulates DNA-templated transcription as a transcription 
      factor.
    action: ACCEPT
    reason: Core function consistent with ELT-2's role as a transcription 
      factor.
- term:
    id: GO:0006355
    label: regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ELT-2 regulates transcription of intestinal genes.
    action: ACCEPT
    reason: Accurate. ELT-2 is a transcriptional regulator controlling 
      expression of intestinal genes.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ELT-2 regulates RNA polymerase II-dependent transcription.
    action: ACCEPT
    reason: Accurate. ELT-2 is a transcription factor that regulates Pol II 
      transcription.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: ELT-2 contains a GATA-type zinc finger domain that coordinates zinc
      for DNA binding.
    action: ACCEPT
    reason: ELT-2 has a conserved GATA-type zinc finger domain (amino acids 
      237-261 per UniProt) that requires zinc for function.
- term:
    id: GO:0009888
    label: tissue development
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: ELT-2 is essential for intestinal (tissue) development.
    action: MODIFY
    reason: While accurate, this term is too general. ELT-2 specifically 
      regulates endoderm/intestinal development.
    proposed_replacement_terms:
    - id: GO:0007492
      label: endoderm development
- term:
    id: GO:0030154
    label: cell differentiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ELT-2 is required for terminal differentiation of intestinal cells.
    action: ACCEPT
    reason: ELT-2 controls intestinal cell differentiation, though a more 
      specific term could be used.
- term:
    id: GO:0043565
    label: sequence-specific DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ELT-2 binds specifically to WGATAR sequences.
    action: ACCEPT
    reason: Well-established that ELT-2 binds DNA in a sequence-specific manner 
      (PMID:10518545, PMID:15733671).
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ELT-2 binds zinc through its GATA zinc finger domain.
    action: ACCEPT
    reason: Accurate but general. The more specific GO:0008270 (zinc ion 
      binding) is also annotated.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:16968778
  review:
    summary: PMID:16968778 demonstrates ELT-2 is required for transcriptional 
      activation of immune response genes in the intestine during P. aeruginosa 
      infection. RNAi knockdown of elt-2 prevents induction of immune genes.
    action: ACCEPT
    reason: Strong experimental evidence from mutant phenotype analysis showing 
      ELT-2 positively regulates transcription of immune response genes.
    supported_by:
    - reference_id: PMID:16968778
      supporting_text: Gene expression and functional RNAi-based analyses 
        identified the tissue-specific GATA transcription factor ELT-2 as a 
        major regulator of an early intestinal protective response to infection 
        with the human bacterial pathogen Pseudomonas aeruginosa.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:20126308
  review:
    summary: Nuclear localization of ELT-2 is well established from multiple 
      studies using ELT-2::GFP fusion proteins that show discrete fluorescent 
      foci within intestinal cell nuclei.
    action: ACCEPT
    reason: Direct experimental evidence of nuclear localization from multiple 
      studies. The PMID:20126308 reference is primarily about osmotic stress 
      responses, but nuclear localization of ELT-2 is well supported by 
      PMID:10518545.
    supported_by:
    - reference_id: PMID:10518545
      supporting_text: the majority of these embryonic gut nuclei show two 
        discrete intense foci of fluorescence
    - reference_id: PMID:20126308
      supporting_text: Genetic and physiological activation of osmosensitive 
        gene expression mimics transcriptional signatures of pathogen infection 
        in C.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:20126308
  review:
    summary: PMID:20126308 shows ELT-2 is required for transcriptional 
      activation of osmotic stress response genes in the intestine.
    action: ACCEPT
    reason: Experimental evidence showing ELT-2 activates transcription of 
      osmosensitive genes through GATA binding sites.
    supported_by:
    - reference_id: PMID:20126308
      supporting_text: RNAi against one GATA factor, elt-2, attenuated 
        osmotically induced GFP expression in the intestine without 
        substantially affecting hypodermal GFP expression
- term:
    id: GO:0008340
    label: determination of adult lifespan
  evidence_type: IMP
  original_reference_id: PMID:24834345
  review:
    summary: PMID:24834345 demonstrates ELT-2 regulates lifespan through 
      transcriptional control of daf-16 isoforms in the intestine.
    action: KEEP_AS_NON_CORE
    reason: While ELT-2 does influence lifespan through regulation of daf-16, 
      this is a downstream consequence of its core transcriptional regulatory 
      function in the intestine, not its primary biological role.
    supported_by:
    - reference_id: PMID:24834345
      supporting_text: we identify elt-2 (GATA transcription factor) and swsn-1 
        (core subunit of SWI/SNF complex) as key modulators of daf-16d/f gene 
        expression. ELT-2 and another GATA factor, ELT-4, promote longevity via 
        both DAF-16a and DAF-16d/f
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:24834345
  review:
    summary: PMID:24834345 shows ELT-2 activates transcription of daf-16 
      isoforms.
    action: ACCEPT
    reason: Direct experimental evidence of ELT-2 positively regulating 
      transcription of daf-16 genes.
    supported_by:
    - reference_id: PMID:24834345
      supporting_text: ELT-2 and another GATA factor, ELT-4, are required for 
        the expression of both daf-16a and daf-16d/f
- term:
    id: GO:0000978
    label: RNA polymerase II cis-regulatory region sequence-specific DNA binding
  evidence_type: IDA
  original_reference_id: PMID:26963674
  review:
    summary: PMID:26963674 demonstrates direct binding of ELT-2 to the vit-2 
      enhancer element.
    action: ACCEPT
    reason: Direct experimental evidence of ELT-2 binding to specific 
      cis-regulatory sequence.
    supported_by:
    - reference_id: PMID:26963674
      supporting_text: an activator site that we show is the direct target of 
        the intestinal GATA factor ELT-2
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IMP
  original_reference_id: PMID:26963674
  review:
    summary: PMID:26963674 provides evidence ELT-2 functions as a transcription 
      factor regulating the vit-2 enhancer.
    action: ACCEPT
    reason: Experimental evidence of transcription factor activity at vit-2 
      enhancer.
    supported_by:
    - reference_id: PMID:26963674
      supporting_text: A 44-bp region from the vit-2 gene promoter is able 
        largely to reconstitute this tissue-, stage- and 
        sex-specific-expression...an activator site that we show is the direct 
        target of the intestinal GATA factor ELT-2
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:26963674
  review:
    summary: Nuclear localization confirmed by imaging studies.
    action: ACCEPT
    reason: Consistent with other experimental evidence of nuclear localization.
    supported_by:
    - reference_id: PMID:26963674
      supporting_text: 2016 Mar 7. A 44 bp intestine-specific 
        hermaphrodite-specific enhancer from the C.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:26963674
  review:
    summary: ELT-2 activates transcription of vit-2 through direct enhancer 
      binding.
    action: ACCEPT
    reason: Strong experimental evidence of ELT-2 activating vit-2 
      transcription.
    supported_by:
    - reference_id: PMID:26963674
      supporting_text: an activator site that we show is the direct target of 
        the intestinal GATA factor ELT-2
- term:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  evidence_type: IDA
  original_reference_id: PMID:14573471
  review:
    summary: PMID:14573471 characterizes ELT-2 as a transcriptional activator 
      using yeast assays and demonstrates sequence-specific DNA binding.
    action: ACCEPT
    reason: Direct experimental evidence of transcription factor activity.
    supported_by:
    - reference_id: PMID:14573471
      supporting_text: Whereas ELT-2 protein is a strong transcriptional 
        activator in yeast
- term:
    id: GO:0004857
    label: enzyme inhibitor activity
  evidence_type: IDA
  original_reference_id: PMID:29361115
  review:
    summary: PMID:29361115 shows ELT-2 physically interacts with PRMT-1 and 
      inhibits its methyltransferase activity in a dose-dependent manner. This 
      is an unusual non-transcriptional function of ELT-2.
    action: KEEP_AS_NON_CORE
    reason: This is a non-canonical function of ELT-2 distinct from its primary 
      role as a transcription factor. The study demonstrates direct 
      protein-protein interaction between ELT-2 and PRMT-1 leading to inhibition
      of PRMT-1 methyltransferase activity, but this appears to be a specialized
      regulatory mechanism rather than a core function.
    supported_by:
    - reference_id: PMID:29361115
      supporting_text: GST pull-down and co-immunoprecipitation assays 
        demonstrate the interaction between ELT-2 and PRMT-1. Furthermore, we 
        find that ELT-2 interferes with PRMT-1-induced arginine methylation in a
        dose-dependent manner.
- term:
    id: GO:0010468
    label: regulation of gene expression
  evidence_type: IMP
  original_reference_id: PMID:26016853
  review:
    summary: PMID:26016853 demonstrates ELT-2 regulates expression of intestinal
      genes including immune response genes and digestive enzymes.
    action: ACCEPT
    reason: Comprehensive experimental evidence from microarray analysis showing
      ELT-2 regulates hundreds of genes in the adult intestine.
    supported_by:
    - reference_id: PMID:26016853
      supporting_text: 'Microarray analysis identified two ELT-2-regulated gene subsets:
        one, enriched for hydrolytic enzymes, pointed at regulation of constitutive
        digestive functions as a dominant role of adult elt-2; the second was enriched
        for immune genes that are induced in response to Pseudomonas aeruginosa infection.'
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:26016853
  review:
    summary: PMID:26016853 shows ELT-2 is required for immune responses to P. 
      aeruginosa, a Gram-negative bacterium.
    action: ACCEPT
    reason: Strong experimental evidence that ELT-2 controls p38-dependent 
      immune gene induction in response to P. aeruginosa infection.
    supported_by:
    - reference_id: PMID:26016853
      supporting_text: we show that elt-2 controls p38-dependent gene induction,
        cooperating with two p38-activated transcription factors, ATF-7 and 
        SKN-1. This demonstrates a mechanism through which the constitutively 
        nuclear elt-2 can impact induced responses, and play a dominant role in 
        C. elegans immunity.
- term:
    id: GO:0000977
    label: RNA polymerase II transcription regulatory region sequence-specific 
      DNA binding
  evidence_type: IDA
  original_reference_id: PMID:10518545
  review:
    summary: PMID:10518545 directly visualizes ELT-2 binding to its own promoter
      in living embryos using ELT-2::GFP fusion protein.
    action: ACCEPT
    reason: Elegant direct experimental demonstration of ELT-2 binding to 
      regulatory DNA sequences in vivo.
    supported_by:
    - reference_id: PMID:10518545
      supporting_text: We interpret these fluorescent foci as the result of 
        ELT-2::GFP binding directly to its own promoter within nuclei of the 
        developing gut lineage. Numerous control experiments, both genetic and 
        biochemical, all support this conclusion and support the specificity of 
        the binding.
- term:
    id: GO:0000977
    label: RNA polymerase II transcription regulatory region sequence-specific 
      DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15733671
  review:
    summary: PMID:15733671 demonstrates ELT-2 binds to WGATAR site in pho-1 
      promoter.
    action: ACCEPT
    reason: In vitro binding assays and functional analysis confirm ELT-2 
      binding to pho-1 regulatory region.
    supported_by:
    - reference_id: PMID:15733671
      supporting_text: Transgenic analysis of the pho-1 promoter shows that gut 
        expression is critically dependent on a single WGATAR site. The 
        gut-specific GATA factor ELT-2 binds to this site in vitro
- term:
    id: GO:0000977
    label: RNA polymerase II transcription regulatory region sequence-specific 
      DNA binding
  evidence_type: IDA
  original_reference_id: PMID:15734735
  review:
    summary: PMID:15734735 demonstrates ELT-2 binds to GATA motif in spl-1 
      (sphingosine-1-phosphate lyase) promoter.
    action: ACCEPT
    reason: In vitro binding and functional analysis confirm ELT-2 regulation of
      spl-1 through GATA binding site.
    supported_by:
    - reference_id: PMID:15734735
      supporting_text: ELT-2 interacted with the GATA factor-binding motif in 
        vitro and was also capable of driving expression of a Caenorhabditis 
        elegans lyase promoter-beta-galactosidase reporter in a heterologous 
        yeast system.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:15734735
  review:
    summary: PMID:15734735 shows ELT-2 activates sphingosine-1-phosphate lyase 
      gene expression.
    action: ACCEPT
    reason: Experimental evidence of ELT-2 activating spl-1 transcription 
      through direct binding to GATA motif.
    supported_by:
    - reference_id: PMID:15734735
      supporting_text: These studies demonstrate that ELT-2 regulates 
        sphingosine-1-phosphate lyase expression in vivo.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:15734735
  review:
    summary: Mutant analysis supports ELT-2's role in activating spl-1 
      transcription.
    action: ACCEPT
    reason: RNAi knockdown demonstrates ELT-2 is required for spl-1 expression.
    supported_by:
    - reference_id: PMID:15734735
      supporting_text: Knockdown of the gut-specific GATA transcription factor 
        ELT-2 by RNA interference similarly led to loss of reporter expression.
- term:
    id: GO:0002119
    label: nematode larval development
  evidence_type: IMP
  original_reference_id: PMID:21868609
  review:
    summary: PMID:21868609 is primarily about pharyngeal gland morphology but 
      notes that elt-2 RNAi causes highly penetrant L1 lethality, confirming 
      ELT-2's essential role in larval development.
    action: ACCEPT
    reason: The paper confirms that elt-2 RNAi causes L1 lethality, consistent 
      with ELT-2's essential role in larval development established by 
      PMID:9659934.
    supported_by:
    - reference_id: PMID:21868609
      supporting_text: "elt-2(RNAi) gives a highly penetrant (∼100%) L1 lethality
        by feeding"
- term:
    id: GO:0045087
    label: innate immune response
  evidence_type: IMP
  original_reference_id: PMID:16968778
  review:
    summary: PMID:16968778 demonstrates ELT-2 is a major regulator of intestinal
      innate immune responses to P. aeruginosa infection.
    action: ACCEPT
    reason: Strong experimental evidence that ELT-2 is required for innate 
      immune responses in the intestine.
    supported_by:
    - reference_id: PMID:16968778
      supporting_text: Gene expression and functional RNAi-based analyses 
        identified the tissue-specific GATA transcription factor ELT-2 as a 
        major regulator of an early intestinal protective response to infection 
        with the human bacterial pathogen Pseudomonas aeruginosa.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:16968778
  review:
    summary: Nuclear localization confirmed in this study.
    action: ACCEPT
    reason: Consistent with multiple other studies showing nuclear localization.
    supported_by:
    - reference_id: PMID:16968778
      supporting_text: A conserved role for a GATA transcription factor in 
        regulating epithelial innate immune responses.
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: IMP
  original_reference_id: PMID:16968778
  review:
    summary: PMID:16968778 shows ELT-2 is required for defense against P. 
      aeruginosa.
    action: ACCEPT
    reason: Key study establishing ELT-2's role in immune defense against 
      Gram-negative bacteria.
    supported_by:
    - reference_id: PMID:16968778
      supporting_text: In the adult worm, ELT-2 is required specifically for 
        infection responses and survival on pathogen but makes no significant 
        contribution to gene expression associated with intestinal maintenance 
        or to resistance to cadmium, heat, and oxidative stress.
- term:
    id: GO:0050829
    label: defense response to Gram-negative bacterium
  evidence_type: HEP
  original_reference_id: PMID:16968778
  review:
    summary: High-throughput expression data from PMID:16968778 supports ELT-2's
      role in defense response.
    action: ACCEPT
    reason: Microarray expression profiling provides additional evidence for 
      ELT-2's role in immune gene regulation.
    supported_by:
    - reference_id: PMID:16968778
      supporting_text: A conserved role for a GATA transcription factor in 
        regulating epithelial innate immune responses.
- term:
    id: GO:0003700
    label: DNA-binding transcription factor activity
  evidence_type: IMP
  original_reference_id: PMID:14573471
  review:
    summary: PMID:14573471 demonstrates ELT-2 is a transcriptional activator.
    action: ACCEPT
    reason: Experimental evidence from yeast assays showing ELT-2 has 
      transcription factor activity.
    supported_by:
    - reference_id: PMID:14573471
      supporting_text: Whereas ELT-2 protein is a strong transcriptional 
        activator in yeast
- term:
    id: GO:0007492
    label: endoderm development
  evidence_type: IMP
  original_reference_id: PMID:14573471
  review:
    summary: PMID:14573471 discusses ELT-2's role in endoderm/intestinal 
      development.
    action: ACCEPT
    reason: Core developmental function of ELT-2 in endoderm differentiation.
    supported_by:
    - reference_id: PMID:14573471
      supporting_text: The elt-2 gene is expressed only in the intestine and is 
        essential for normal intestinal development.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IDA
  original_reference_id: PMID:14573471
  review:
    summary: Direct demonstration of ELT-2 transcriptional activation activity.
    action: ACCEPT
    reason: Yeast one-hybrid assays directly demonstrate ELT-2 activates 
      transcription.
    supported_by:
    - reference_id: PMID:14573471
      supporting_text: Whereas ELT-2 protein is a strong transcriptional 
        activator in yeast, ELT-4 protein has no such activity under similar 
        conditions
- term:
    id: GO:0002119
    label: nematode larval development
  evidence_type: IMP
  original_reference_id: PMID:9659934
  review:
    summary: PMID:9659934 shows elt-2 null mutants die at L1 stage, 
      demonstrating essential role in larval development.
    action: ACCEPT
    reason: elt-2 is essential for larval survival and development - null 
      mutants arrest at L1 stage.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: Homozygous elt-2 null mutants die at the L1 larval stage 
        with an apparent malformation or degeneration of gut cells.
- term:
    id: GO:0003690
    label: double-stranded DNA binding
  evidence_type: IDA
  original_reference_id: PMID:14573471
  review:
    summary: PMID:14573471 demonstrates ELT-2 binds to double-stranded DNA 
      containing GATA sequences.
    action: ACCEPT
    reason: In vitro binding experiments confirm ELT-2 binds dsDNA.
    supported_by:
    - reference_id: PMID:14573471
      supporting_text: In vitro binding experiments could not detect specific 
        binding of ELT-4 protein to candidate binding sites (double-stranded 
        oligonucleotides containing single or multiple WGATAR sequences); ELT-4 
        protein neither enhanced nor inhibited the strong sequence-specific 
        binding of the ELT-2 protein.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:9659934
  review:
    summary: Original study demonstrating ELT-2 nuclear localization.
    action: ACCEPT
    reason: Key early evidence of nuclear localization of ELT-2.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: The GATA-factor elt-2 is essential for formation of the 
        Caenorhabditis elegans intestine.
- term:
    id: GO:0007492
    label: endoderm development
  evidence_type: IMP
  original_reference_id: PMID:9659934
  review:
    summary: PMID:9659934 establishes ELT-2 as essential for intestinal/endoderm
      development.
    action: ACCEPT
    reason: Foundational study establishing ELT-2's essential role in endoderm 
      development.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: Homozygous elt-2 null mutants die at the L1 larval stage 
        with an apparent malformation or degeneration of gut cells.
- term:
    id: GO:0007586
    label: digestion
  evidence_type: IMP
  original_reference_id: PMID:9659934
  review:
    summary: PMID:9659934 shows elt-2 null mutants have defective intestinal 
      function. PMID:26016853 demonstrates ELT-2 regulates expression of 
      hydrolytic enzymes involved in constitutive digestive functions in the 
      adult intestine.
    action: ACCEPT
    reason: ELT-2 regulates expression of digestive enzymes in the intestine and
      loss of elt-2 leads to digestive defects. Microarray analysis confirms 
      ELT-2 controls hydrolytic enzyme expression.
    supported_by:
    - reference_id: PMID:26016853
      supporting_text: one, enriched for hydrolytic enzymes, pointed at 
        regulation of constitutive digestive functions as a dominant role of 
        adult elt-2
    - reference_id: PMID:9659934
      supporting_text: The GATA-factor elt-2 is essential for formation of the 
        Caenorhabditis elegans intestine.
    additional_reference_ids:
    - PMID:9659934
- term:
    id: GO:0030856
    label: regulation of epithelial cell differentiation
  evidence_type: IMP
  original_reference_id: PMID:9659934
  review:
    summary: ELT-2 regulates differentiation of intestinal epithelial cells.
    action: ACCEPT
    reason: ELT-2 controls terminal differentiation of intestinal epithelial 
      cells.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: loss of elt-2 function has major consequences for later 
        gut morphogenesis and function
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:9659934
  review:
    summary: PMID:9659934 shows ectopic ELT-2 expression activates ges-1 
      transcription.
    action: ACCEPT
    reason: Ectopic expression experiments demonstrate ELT-2 activates 
      transcription of intestinal genes.
    supported_by:
    - reference_id: PMID:9659934
      supporting_text: When elt-2 is expressed ectopically using a transgenic 
        heat-shock construct, the endogenous ges-1 gene is now expressed in most
        if not all cells of the embryo
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with 
    GO terms
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: ELT-2 belongs to the GATA transcription factor family with 
      conserved DNA-binding and transcriptional regulatory functions
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning 
    models
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
- id: PMID:9659934
  title: The GATA-factor elt-2 is essential for formation of the Caenorhabditis 
    elegans intestine.
  findings:
  - statement: ELT-2 is essential for intestinal development
    supporting_text: The GATA-factor elt-2 is essential for formation of the 
      Caenorhabditis elegans intestine.
  - statement: elt-2 null mutants die at L1 larval stage with malformed gut 
      cells
    supporting_text: The GATA-factor elt-2 is essential for formation of the 
      Caenorhabditis elegans intestine.
  - statement: elt-2 is expressed gut-specifically from 2E cell stage through 
      adulthood
    supporting_text: The GATA-factor elt-2 is essential for formation of the 
      Caenorhabditis elegans intestine.
  - statement: Ectopic elt-2 expression causes ectopic ges-1 expression
    supporting_text: The GATA-factor elt-2 is essential for formation of the 
      Caenorhabditis elegans intestine.
  - statement: ELT-2 likely autoregulates its own promoter
    supporting_text: The GATA-factor elt-2 is essential for formation of the 
      Caenorhabditis elegans intestine.
- id: PMID:10518545
  title: Direct visualization of the elt-2 gut-specific GATA factor binding to a
    target promoter inside the living Caenorhabditis elegans embryo.
  findings:
  - statement: ELT-2::GFP binds to elt-2 promoter in discrete nuclear foci in 
      living embryos
    supporting_text: Direct visualization of the elt-2 gut-specific GATA factor 
      binding to a target promoter inside the living Caenorhabditis elegans 
      embryo.
  - statement: ELT-2 directly autoregulates its own promoter
    supporting_text: Direct visualization of the elt-2 gut-specific GATA factor 
      binding to a target promoter inside the living Caenorhabditis elegans 
      embryo.
  - statement: Demonstrates sequence-specific DNA binding in vivo
    supporting_text: Direct visualization of the elt-2 gut-specific GATA factor 
      binding to a target promoter inside the living Caenorhabditis elegans 
      embryo.
- id: PMID:14573471
  title: The evolutionary duplication and probable demise of an endodermal GATA 
    factor in Caenorhabditis elegans.
  findings:
  - statement: ELT-2 is a strong transcriptional activator in yeast assays
    supporting_text: The evolutionary duplication and probable demise of an 
      endodermal GATA factor in Caenorhabditis elegans.
  - statement: ELT-2 binds specifically to WGATAR sequences in vitro
    supporting_text: The evolutionary duplication and probable demise of an 
      endodermal GATA factor in Caenorhabditis elegans.
  - statement: ELT-4 is a duplicated but apparently non-functional paralog
    supporting_text: The evolutionary duplication and probable demise of an 
      endodermal GATA factor in Caenorhabditis elegans.
- id: PMID:15733671
  title: Transcriptional control and patterning of the pho-1 gene, an essential 
    acid phosphatase expressed in the C. elegans intestine.
  findings:
  - statement: pho-1 is a direct target of ELT-2
    supporting_text: Transcriptional control and patterning of the pho-1 gene, 
      an essential acid phosphatase expressed in the C. elegans intestine.
  - statement: ELT-2 binds to WGATAR site in pho-1 promoter in vitro
    supporting_text: Transcriptional control and patterning of the pho-1 gene, 
      an essential acid phosphatase expressed in the C. elegans intestine.
  - statement: Loss of ELT-2 destroys pho-1 reporter expression
    supporting_text: Transcriptional control and patterning of the pho-1 gene, 
      an essential acid phosphatase expressed in the C. elegans intestine.
- id: PMID:15734735
  title: Regulation of sphingosine-1-phosphate lyase gene expression by members 
    of the GATA family of transcription factors.
  findings:
  - statement: ELT-2 regulates sphingosine-1-phosphate lyase (spl-1) expression
    supporting_text: Regulation of sphingosine-1-phosphate lyase gene expression
      by members of the GATA family of transcription factors.
  - statement: ELT-2 binds GATA motif in spl-1 promoter
    supporting_text: Regulation of sphingosine-1-phosphate lyase gene expression
      by members of the GATA family of transcription factors.
  - statement: ELT-2 can activate spl-1 promoter in yeast system
    supporting_text: Regulation of sphingosine-1-phosphate lyase gene expression
      by members of the GATA family of transcription factors.
- id: PMID:16968778
  title: A conserved role for a GATA transcription factor in regulating 
    epithelial innate immune responses.
  findings:
  - statement: ELT-2 is major regulator of intestinal immune responses to P. 
      aeruginosa
    supporting_text: A conserved role for a GATA transcription factor in 
      regulating epithelial innate immune responses.
  - statement: Required for infection responses and survival on pathogen
    supporting_text: A conserved role for a GATA transcription factor in 
      regulating epithelial innate immune responses.
  - statement: Function is conserved - human GATA6 has similar protective role
    supporting_text: A conserved role for a GATA transcription factor in 
      regulating epithelial innate immune responses.
  - statement: ELT-2 does not contribute to resistance to cadmium, heat, or 
      oxidative stress
    supporting_text: A conserved role for a GATA transcription factor in 
      regulating epithelial innate immune responses.
- id: PMID:20126308
  title: Genetic and physiological activation of osmosensitive gene expression 
    mimics transcriptional signatures of pathogen infection in C. elegans.
  findings:
  - statement: ELT-2 mediates osmosensitive gene expression in intestine
    supporting_text: Genetic and physiological activation of osmosensitive gene 
      expression mimics transcriptional signatures of pathogen infection in C. 
      elegans.
  - statement: Works with ELT-3 (hypodermal) for organismal osmotic stress 
      resistance
    supporting_text: Genetic and physiological activation of osmosensitive gene 
      expression mimics transcriptional signatures of pathogen infection in C. 
      elegans.
  - statement: GATA binding sites required for osmosensitive gene activation
    supporting_text: Genetic and physiological activation of osmosensitive gene 
      expression mimics transcriptional signatures of pathogen infection in C. 
      elegans.
- id: PMID:24834345
  title: Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 
    modulates lifespan.
  findings:
  - statement: ELT-2 regulates daf-16d/f isoform expression in intestine
    supporting_text: Transcriptional regulation of Caenorhabditis elegans 
      FOXO/DAF-16 modulates lifespan.
  - statement: Required for daf-16 expression and lifespan extension
    supporting_text: Transcriptional regulation of Caenorhabditis elegans 
      FOXO/DAF-16 modulates lifespan.
  - statement: ELT-2 and ELT-4 promote longevity via DAF-16a and DAF-16d/f
    supporting_text: Transcriptional regulation of Caenorhabditis elegans 
      FOXO/DAF-16 modulates lifespan.
- id: PMID:26016853
  title: The Developmental Intestinal Regulator ELT-2 Controls p38-Dependent 
    Immune Responses in Adult C. elegans.
  findings:
  - statement: ELT-2 controls p38-dependent immune gene induction
    supporting_text: The Developmental Intestinal Regulator ELT-2 Controls 
      p38-Dependent Immune Responses in Adult C. elegans.
  - statement: Cooperates with ATF-7 and SKN-1 downstream of p38
    supporting_text: The Developmental Intestinal Regulator ELT-2 Controls 
      p38-Dependent Immune Responses in Adult C. elegans.
  - statement: Regulates constitutive digestive enzyme expression in adults
    supporting_text: The Developmental Intestinal Regulator ELT-2 Controls 
      p38-Dependent Immune Responses in Adult C. elegans.
  - statement: Essential for both basal and induced immune gene expression
    supporting_text: The Developmental Intestinal Regulator ELT-2 Controls 
      p38-Dependent Immune Responses in Adult C. elegans.
- id: PMID:26963674
  title: A 44 bp intestine-specific hermaphrodite-specific enhancer from the C. 
    elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-9
    and DAF-16.
  findings:
  - statement: ELT-2 directly binds and activates 44bp vit-2 enhancer
    supporting_text: A 44 bp intestine-specific hermaphrodite-specific enhancer 
      from the C. elegans vit-2 vitellogenin gene is directly regulated by 
      ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, 
      by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway.
  - statement: Works with MAB-3, FKH-9, and DAF-16 to regulate vit-2
    supporting_text: A 44 bp intestine-specific hermaphrodite-specific enhancer 
      from the C. elegans vit-2 vitellogenin gene is directly regulated by 
      ELT-2, MAB-3, FKH-9 and DAF-16 and indirectly regulated by the germline, 
      by daf-2/insulin signaling and by the TGF-β/Sma/Mab pathway.
- id: PMID:29361115
  title: The GATA transcription factor ELT-2 modulates both the expression and 
    methyltransferase activity of PRMT-1 in Caenorhabditis elegans.
  findings:
  - statement: ELT-2 regulates prmt-1 expression transcriptionally
    supporting_text: The GATA transcription factor ELT-2 modulates both the 
      expression and methyltransferase activity of PRMT-1 in Caenorhabditis 
      elegans.
  - statement: ELT-2 physically interacts with PRMT-1 protein
    supporting_text: The GATA transcription factor ELT-2 modulates both the 
      expression and methyltransferase activity of PRMT-1 in Caenorhabditis 
      elegans.
  - statement: ELT-2 inhibits PRMT-1 methyltransferase activity through protein 
      interaction
    supporting_text: The GATA transcription factor ELT-2 modulates both the 
      expression and methyltransferase activity of PRMT-1 in Caenorhabditis 
      elegans.
- id: PMID:21868609
  title: 'Cell architecture: surrounding muscle cells shape gland cell morphology
    in the Caenorhabditis elegans pharynx.'
  findings:
  - statement: Used elt-2::GFP as marker for intestinal cells
    supporting_text: 'Cell architecture: surrounding muscle cells shape gland cell
      morphology in the Caenorhabditis elegans pharynx.'
  - statement: Not a direct study of elt-2 function
    supporting_text: 'Cell architecture: surrounding muscle cells shape gland cell
      morphology in the Caenorhabditis elegans pharynx.'
- id: file:worm/elt-2/elt-2-deep-research-falcon.md
  title: Deep research report on elt-2
  findings: []
core_functions:
- description: ELT-2 is a GATA-type transcription factor that binds to WGATAR 
    sequences and activates transcription of intestinal genes. Demonstrated 
    through in vitro binding, yeast activation assays, and in vivo visualization
    (PMID:10518545, PMID:14573471, PMID:15733671, PMID:15734735).
  molecular_function:
    id: GO:0000981
    label: DNA-binding transcription factor activity, RNA polymerase II-specific
  directly_involved_in:
  - id: GO:0007492
    label: endoderm development
  - id: GO:0045087
    label: innate immune response
  - id: GO:0007586
    label: digestion
  locations:
  - id: GO:0005634
    label: nucleus
tags:
- caeel-surveillance-immunity

elt-2

Gene Description

Existing Annotations Review

Core Functions

ELT-2 is a GATA-type transcription factor that binds to WGATAR sequences and activates transcription of intestinal genes. Demonstrated through in vitro binding, yeast activation assays, and in vivo visualization (PMID:10518545, PMID:14573471, PMID:15733671, PMID:15734735).

References

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Gene Research for Functional Annotation

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