gtaC

UniProt ID: Q75JZ1
Organism: Dictyostelium discoideum
Review Status: COMPLETE
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Gene Description

GtaC is a GATA-family transcription factor of Dictyostelium discoideum that carries a single Cys2-Cys2 (type IV) zinc-finger domain and binds sequence-specific GATA-like cis-regulatory elements in the promoters of target genes. It is a nuclear DNA-binding transcription factor that activates and represses developmental gene expression, and it is essential for early development, since cells lacking gtaC fail to aggregate and arrest transcriptional and morphological progression. GtaC is a central effector that decodes oscillatory extracellular cAMP signals. During early development it undergoes rapid nucleocytoplasmic shuttling driven by cAMP-receptor occupancy and reversible phosphorylation (mediated by the atypical MAPK Erk2 and GskA), entering the nucleus during the falling phase of each cAMP wave and exiting during the rising phase. This shuttling converts pulsatile cAMP input into temporally patterned bursts of transcription and functions as a developmental timer, allowing cells to track low-frequency and filter out high-frequency signals. GtaC directly binds the promoters of thousands of genes, including central cAMP-signalling components such as the adenylyl cyclase acaA and cAMP receptor carA, and its DNA binding is highly dynamic across developmental stages. Beyond aggregation, GtaC contributes to later cell-type specification, acting downstream of the diffusible morphogen DIF-1 to regulate prestalk/basal-disc (stalk-related) differentiation, and it modulates chemotactic behaviour, suppressing chemotaxis toward folate.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000976 transcription cis-regulatory region binding
IBA
GO_REF:0000033
ACCEPT
Summary: Phylogenetic inference that GtaC binds cis-regulatory regions is correct and independently confirmed by direct ChIP-seq evidence in the same organism, where GtaC occupies GATA-like promoter elements genome-wide.
Reason: This IBA annotation transfers the conserved GATA-family DNA-binding function and is fully corroborated by direct experimental evidence (ChIP-seq) showing GtaC binds thousands of promoters at a GATA-like motif. This is a core molecular function.
Supporting Evidence:
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
PMID:26144553
We identified 2,091 genes whose promoter regions were bound by GtaC
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: Nuclear localization inferred by phylogeny is correct; GtaC acts as a transcription factor in the nucleus and multiple direct studies show nuclear accumulation.
Reason: As a DNA-binding transcription factor, GtaC is active in the nucleus. This is directly supported by localization studies of GFP-GtaC.
Supporting Evidence:
PMID:24653039
GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling during early development
GO:0006357 regulation of transcription by RNA polymerase II
IBA
GO_REF:0000033
ACCEPT
Summary: GtaC regulates developmental gene expression by binding promoter cis-regulatory elements and modulating transcription of target genes, so involvement in regulation of RNA polymerase II transcription is well founded.
Reason: Direct target identification (integrated ChIP-seq and RNA-seq) shows GtaC binding to promoters is associated with both up- and downregulation of target gene expression, establishing it as a bona fide transcriptional regulator. This is a core biological process.
Supporting Evidence:
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO inference of transcriptional regulation from the GATA zinc-finger domain is correct but is a more general parent of the RNA polymerase II term already annotated.
Reason: The annotation is biologically accurate (GtaC regulates DNA-templated transcription) but is a less specific parent of GO:0006357 (regulation of transcription by RNA polymerase II), which is also annotated. It is retained as correct though non-preferred relative to the more specific term.
Supporting Evidence:
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0008270 zinc ion binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: The GATA-type Cys2-Cys2 zinc finger of GtaC coordinates a zinc ion that is required for DNA binding, so zinc ion binding is correct but is a supporting activity rather than the core function.
Reason: GtaC contains a Cys2-Cys2 (type IV) GATA zinc finger whose structural zinc ion is required for sequence-specific DNA binding. The annotation is accurate but represents an underlying structural activity that enables the core DNA-binding transcription-factor function rather than a function in its own right.
Supporting Evidence:
PMID:26144553
mediates DNA binding with a zinc ion
GO:0043565 sequence-specific DNA binding
IEA
GO_REF:0000002
ACCEPT
Summary: GtaC binds a specific GATA-like DNA motif, as shown directly by ChIP-seq motif enrichment, so sequence-specific DNA binding is correct.
Reason: The InterPro2GO inference of sequence-specific DNA binding is directly confirmed by ChIP-seq, which identified enrichment of a GATA-like motif only in GtaC-bound regions. This underpins its transcription-factor activity.
Supporting Evidence:
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
GO:0003700 DNA-binding transcription factor activity
IMP
PMID:39672161
Collective oscillatory signaling in Dictyostelium discoideum...
ACCEPT
Summary: GtaC is a DNA-binding transcription factor essential for developmental gene expression; this is a core molecular function established by multiple experimental studies.
Reason: The full text of PMID:39672161 is not available in the cache, but GtaC's identity as a DNA-binding transcription factor is firmly established by direct ChIP-seq and genetic evidence in other studies. Per repository policy the experimental (IMP) curator annotation is retained; the function is independently corroborated below.
Supporting Evidence:
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
PMID:24653039
The insertion occurred in the second exon of the gtaC gene, which encodes a GATA family zinc finger transcription factor
GO:0005634 nucleus
IDA
PMID:39672161
Collective oscillatory signaling in Dictyostelium discoideum...
ACCEPT
Summary: Nuclear localization of GtaC is directly demonstrated; GtaC acts as a transcription factor in the nucleus.
Reason: GtaC nuclear localization is directly observed (GFP-GtaC accumulates in the nucleus). Although the cited paper's full text is uncached, nuclear activity is well established by multiple direct studies.
Supporting Evidence:
PMID:24653039
GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling during early development
GO:0005829 cytosol
IDA
PMID:39672161
Collective oscillatory signaling in Dictyostelium discoideum...
ACCEPT
Summary: GtaC is found in the cytoplasm/cytosol during the cytoplasmic phase of its cAMP-driven nucleocytoplasmic shuttling.
Reason: GtaC shuttles between nucleus and cytoplasm; upon cAMP-receptor occupancy it exits the nucleus into the cytosol. Cytosolic localization is part of its normal shuttling behaviour and is directly documented.
Supporting Evidence:
PMID:24653039
GtaC shifted from the nucleus to the cytoplasm with a half-life of ~65 s
GO:0005634 nucleus
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
ACCEPT
Summary: Direct imaging of GFP-GtaC demonstrates nuclear localization during early development, where GtaC acts as a transcription factor.
Reason: Cai et al. 2014 directly visualized GtaC oscillating into the nucleus during early development, consistent with its role as a nuclear transcription factor. This is a core localization.
Supporting Evidence:
PMID:24653039
GFP-GtaC underwent oscillatory nucleocytoplasmic shuttling during early development
GO:0005737 cytoplasm
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
ACCEPT
Summary: GtaC directly localizes to the cytoplasm during the cytoplasmic phase of its cAMP-driven shuttling cycle.
Reason: Cai et al. 2014 directly showed GtaC moving from nucleus to cytoplasm in response to cAMP-receptor occupancy. Cytoplasmic localization is an intrinsic part of the shuttling mechanism.
Supporting Evidence:
PMID:24653039
GtaC shifted from the nucleus to the cytoplasm with a half-life of ~65 s
GO:0043326 chemotaxis to folate
IMP
PMID:35916164
An atypical MAPK regulates translocation of a GATA transcrip...
KEEP AS NON CORE
Summary: Loss of GtaC enhances chemotactic movement toward folate, indicating GtaC negatively modulates folate chemotaxis; it acts upstream of this foraging process.
Reason: Hadwiger et al. 2022 showed that gtaC-null cells have enhanced folate chemotaxis, so GtaC influences (suppresses) this foraging response. The annotation is experimentally supported, but this modulatory foraging role is peripheral to GtaC's core function as a developmental transcription factor.
Supporting Evidence:
PMID:35916164
Loss of GtaC function resulted in enhanced chemotactic movement to folate, suggesting that GtaC suppresses responses to folate.
PMID:35916164
Erk2 was also found to be essential for the translocation of GtaC in response to external folate, a foraging signal that directs the chemotaxis of amoeba to bacteria.
GO:0140582 adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
KEEP AS NON CORE
Summary: GtaC is a downstream effector within the cAMP-receptor signalling pathway; its shuttling is driven by cAMP-receptor occupancy and it regulates expression of core cAMP-signalling genes such as acaA and carA.
Reason: GtaC participates in the cAMP GPCR signalling relay - its nucleocytoplasmic shuttling is driven by cAMP-receptor occupancy and it decodes cAMP pulses to regulate expression of cAMP-signalling components. The annotation captures a genuine signalling role, but the core molecular function of GtaC is transcriptional regulation, so this is retained as non-core.
Supporting Evidence:
PMID:24653039
nucleocytoplasmic shuttling of GtaC is driven by periodic occupancy of the surface receptor from self-organized cAMP oscillations.
PMID:26144553
GtaC is a key regulator that decodes extracellular cAMP pulses and establishes downstream signalling pathways, ensuring timely development.
GO:0000976 transcription cis-regulatory region binding
IDA
PMID:26144553
The GATA transcription factor GtaC regulates early developme...
ACCEPT
Summary: Direct ChIP-seq evidence demonstrates GtaC binds cis-regulatory promoter regions at a GATA-like motif genome-wide. This is a core molecular function.
Reason: Santhanam et al. 2015 provided direct genome-wide evidence that GtaC binds thousands of promoter cis-regulatory regions, with enrichment for a GATA-like motif specifically in wild-type GtaC-bound regions. This is the strongest support for GtaC's core DNA-binding function.
Supporting Evidence:
PMID:26144553
We identified 2,091 genes whose promoter regions were bound by GtaC
PMID:26144553
We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
GO:0003700 DNA-binding transcription factor activity
IDA
PMID:26144553
The GATA transcription factor GtaC regulates early developme...
ACCEPT
Summary: GtaC binds specific promoter motifs and its binding is directly associated with up- and downregulation of target genes, establishing DNA-binding transcription factor activity. This is a core molecular function.
Reason: Integration of ChIP-seq and RNA-seq directly demonstrates that GtaC binding to GATA-like sequences regulates target gene expression, confirming its DNA-binding transcription-factor activity.
Supporting Evidence:
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0005634 nucleus
IDA
PMID:18367552
Cell type specificity of a diffusible inducer is determined ...
ACCEPT
Summary: GtaC translocates to the nucleus (in response to the morphogen DIF), consistent with its role as a nuclear transcription factor.
Reason: Keller and Thompson 2008 directly showed GtaC rapidly translocating to the nucleus in response to DIF, supporting nuclear activity as a transcription factor.
Supporting Evidence:
PMID:18367552
GtaC rapidly translocates to the nucleus in response to DIF
GO:0005737 cytoplasm
IDA
PMID:18367552
Cell type specificity of a diffusible inducer is determined ...
ACCEPT
Summary: GtaC is cytoplasmic prior to signal-induced nuclear translocation, consistent with its regulated nucleocytoplasmic distribution.
Reason: In the DIF-signalling context, GtaC resides in the cytoplasm and translocates to the nucleus upon stimulation, consistent with its signal-regulated shuttling behaviour documented elsewhere.
Supporting Evidence:
PMID:18367552
GtaC rapidly translocates to the nucleus in response to DIF
GO:0006351 DNA-templated transcription
IDA
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
MODIFY
Summary: GtaC regulates transcription of target genes but does not itself perform DNA-templated transcription (it is a transcription factor, not the polymerase). The regulatory term is more appropriate.
Reason: GO:0006351 (DNA-templated transcription) denotes the catalytic process of synthesizing RNA from a DNA template, an activity of RNA polymerase, not of a sequence-specific transcription factor. GtaC controls the expression of target genes by binding cis-regulatory elements, so the regulatory term regulation of transcription by RNA polymerase II better captures its role.
Supporting Evidence:
PMID:24653039
receptor occupancy promotes nuclear exit of GtaC, which leads to a transient burst of transcription at each cAMP cycle
PMID:26144553
GtaC binding to GATA-like sequences has a direct role in upregulating gene expression
GO:0060176 regulation of aggregation involved in sorocarp development
IMP
PMID:24653039
Nucleocytoplasmic shuttling of a GATA transcription factor f...
ACCEPT
Summary: gtaC-null cells are defective in aggregation and cannot progress through early development, establishing GtaC as an upstream regulator of aggregation during sorocarp development. This is a core developmental role.
Reason: Loss of gtaC impairs aggregation and arrests morphological and transcriptional progression; expression of GFP-GtaC rescues these defects. This directly places GtaC upstream of aggregation during sorocarp development.
Supporting Evidence:
PMID:26144553
Cells lacking gtaC are defective in aggregation and in morphological and transcriptional progression.
PMID:24653039
GtaC shuttling is required for proper control of developmental gene expression and development progression.
GO:0031152 aggregation involved in sorocarp development
IEP
PMID:25887420
Leaps and lulls in the developmental transcriptome of Dictyo...
KEEP AS NON CORE
Summary: gtaC transcript abundance is developmentally regulated with a peak during the aggregation phase, and gtaC is described as a master transcriptional regulator of aggregation-associated genes; this expression-pattern annotation is consistent with its established aggregation role.
Reason: The IEP annotation is based on gtaC's developmental expression profile, which peaks during aggregation, and its identification as a master regulator of aggregation genes. It corroborates GtaC's aggregation role but, being derived from an expression pattern, is retained as non-core relative to the direct genetic and molecular evidence (GO:0060176).
Supporting Evidence:
PMID:25887420
The master transcriptional regulator gtaC, and several of its putative target genes involved in aggregation (such as the cell-cell adhesion gene csaA), looked markedly different at different time scales
GO:0031149 sorocarp stalk cell differentiation
IMP
PMID:18367552
Cell type specificity of a diffusible inducer is determined ...
KEEP AS NON CORE
Summary: GtaC acts downstream of the morphogen DIF-1 to regulate prestalk (pstB) and basal-disc cell differentiation, a stalk-lineage cell-type role that is secondary to its core early-developmental transcriptional function.
Reason: Keller and Thompson 2008 showed that GtaC is required for DIF-dependent pstB and basal-disc (stalk-lineage) differentiation. The annotation is experimentally supported but represents a later, cell-type-specific role that is peripheral to GtaC's core function in early developmental gene regulation.
Supporting Evidence:
PMID:18367552
GtaC is instead required to regulate DIF-dependent pstB and basal disc cell differentiation.
PMID:18367552
gtaC expression is directly regulated by DIF, and GtaC rapidly translocates to the nucleus in response to DIF.

Core Functions

GtaC is a sequence-specific GATA-family transcription factor that binds GATA-like cis-regulatory elements in target-gene promoters via its Cys2-Cys2 zinc-finger domain, directly controlling developmental gene expression by both activating and repressing target genes.

Supporting Evidence:
  • PMID:26144553
    We found enrichment for a GATA-like motif only in regions bound by the WT GtaC
  • PMID:26144553
    GtaC binding to GATA-like sequences has a direct role in upregulating gene expression

GtaC binds cis-regulatory promoter regions genome-wide and is essential for early development, acting upstream of aggregation; through cAMP-driven nucleocytoplasmic shuttling it decodes oscillatory cAMP pulses to time developmental gene expression.

Supporting Evidence:
  • PMID:26144553
    We identified 2,091 genes whose promoter regions were bound by GtaC
  • PMID:26144553
    Cells lacking gtaC are defective in aggregation and in morphological and transcriptional progression.
  • PMID:24653039
    nucleocytoplasmic shuttling of GtaC is driven by periodic occupancy of the surface receptor from self-organized cAMP oscillations.

References

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