DVE-1 is a homeodomain-containing transcription factor orthologous to Drosophila defective proventriculus (Dve) and mammalian SATB family proteins. It functions as a chromatin-associated regulator essential for the mitochondrial unfolded protein response (UPR-mt). DVE-1 forms a complex with UBL-5 and interacts with chromatin modifiers including HDA-1 (HDAC1/2 ortholog), the NuRD complex (via LIN-40), and histone methyltransferase MET-2. Upon mitochondrial stress, DVE-1 translocates from cytosol to nucleus where it binds promoters of mitochondrial chaperone genes (hsp-6, hsp-60) to enable their transcriptional activation. SUMOylation at K327 regulates DVE-1 subcellular localization, with desumoylation by ULP-4 required for nuclear accumulation. Beyond UPR-mt, DVE-1 regulates thousands of genes involved in innate immunity, lipid metabolism, and longevity, often independently of the canonical ATFS-1 pathway. Recent work reveals additional roles in developmental synapse elimination in GABAergic neurons. DVE-1 is essential for embryonic development.
Definition: Any process that modulates the frequency, rate or extent of the mitochondrial unfolded protein response, the series of molecular signals generated as a consequence of the presence of unfolded proteins in the mitochondrial matrix.
Justification: GO:0034514 (mitochondrial unfolded protein response) exists, but a regulatory term would better capture DVE-1's role as a transcriptional regulator rather than the response itself. Terms like GO:0036499 (regulation of IRE1-mediated UPR) exist for ER-UPR but not for UPR-mt.
Parent term: mitochondrial unfolded protein response
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: DVE-1 is a homeodomain-containing transcription factor that regulates RNA polymerase II-dependent transcription of UPR-mt target genes (hsp-6, hsp-60) and thousands of additional genes. The SATB-like domain structure and experimental evidence from reporter assays support this annotation. Reason: The IBA annotation is well-supported by experimental evidence. DVE-1 contains two homeobox DNA-binding domains (UniProt features) and functions as a transcription factor that directly regulates gene expression. PMID:17925224 demonstrates DVE-1 binds to promoters of mitochondrial chaperone genes and is required for their transcriptional activation. PMID:35021096 shows DVE-1 binds to the nhr-80 promoter to transactivate its expression. The phylogenetic inference from SATB family members is consistent with experimental findings. Supporting Evidence: PMID:17925224 Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5 PMID:35021096 The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: DVE-1 regulates transcription of numerous genes by RNA polymerase II, including UPR-mt target genes and genes involved in lipid metabolism, innate immunity, and longevity. Reason: This IBA annotation is supported by extensive experimental evidence. DVE-1 is required for transcriptional activation of hsp-6 and hsp-60 reporters under mitochondrial stress (PMID:17925224). RNA-seq analyses show DVE-1 knockdown affects thousands of genes (deep research report cites ~3,177 genes changed by dve-1 RNAi). DVE-1 also activates nhr-80 transcription linking UPR-mt to lipid metabolism (PMID:35021096). Supporting Evidence: PMID:17925224 Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5 PMID:35021096 Inactivation of DVE-1 or NHR-80 fully abolishes the citrate-induced lipid accumulation |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: DVE-1 contains two homeobox DNA-binding domains and binds to promoter regions of target genes including mitochondrial chaperone genes and nhr-80. Reason: The IBA annotation is consistent with DVE-1's domain structure (two homeobox domains, SATB-like features) and experimental evidence showing DVE-1 binds to promoters of UPR-mt genes (PMID:17925224) and the nhr-80 promoter (PMID:35021096). While a specific consensus DNA binding motif has not been definitively established, the promoter binding activity supports sequence-specific DNA binding. Supporting Evidence: PMID:17925224 Activation of the UPR(mt) correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes PMID:35021096 The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression |
| GO:0006338 chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: DVE-1 participates in chromatin remodeling as part of the UPR-mt response. It associates with the NuRD chromatin remodeling complex and cooperates with chromatin modifiers to enable stress-responsive gene expression. Reason: DVE-1 functions within a chromatin reorganization hub during mitochondrial stress. PMID:32789178 shows DVE-1 associates with the NuRD complex via LIN-40, mediating chromatin remodeling in response to acetyl-CoA levels. PMID:32934238 demonstrates DVE-1 interacts with HDA-1 to regulate chromatin state for UPR-mt gene expression. The SATB family homology further supports genome-organizing functions. Supporting Evidence: PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level PMID:32934238 HDA-1 interacts and coordinates with the genome organizer DVE-1 to induce the transcription of a broad spectrum of UPRmt, innate immune response and metabolic reprogramming genes |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: DVE-1 contains two homeobox DNA-binding domains and binds DNA at promoter regions of target genes. Reason: This IEA annotation is correctly inferred from DVE-1's domain architecture. The protein contains two homeobox domains (UniProt FT DNA_BIND 179-248 and 385-458) which are well-characterized DNA-binding domains. Experimental evidence confirms DVE-1 binds to promoters of mitochondrial chaperone genes (PMID:17925224) and nhr-80 (PMID:35021096). The more specific term GO:0000978 is also annotated. Supporting Evidence: PMID:17925224 Activation of the UPR(mt) correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000117 | ACCEPT | Summary: DVE-1 functions as a DNA-binding transcription factor that regulates expression of UPR-mt genes and many other targets. Reason: This IEA annotation is accurate and supported by experimental evidence. DVE-1 contains homeobox DNA-binding domains and directly activates transcription of target genes. PMID:35021096 explicitly identifies DVE-1 as a transcription factor that transactivates nhr-80 expression. The more specific term GO:0000981 (RNA polymerase II-specific) is also appropriately annotated. Supporting Evidence: PMID:35021096 The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: DVE-1 localizes to the nucleus, particularly under mitochondrial stress conditions when it translocates from cytosol to nucleus. Reason: Nuclear localization of DVE-1 is well-established by multiple experimental studies using DVE-1::GFP reporters. PMID:17925224, PMID:30642431, PMID:32934238, and PMID:32789178 all demonstrate nuclear localization. The IEA inference is correct, though this annotation is superseded by IDA evidence from multiple publications. Supporting Evidence: PMID:17925224 Activation of the UPR(mt) correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: DVE-1 is found in the cytosol under basal conditions and translocates to the nucleus upon mitochondrial stress. SUMOylation at K327 retains DVE-1 in cytosol. Reason: Cytosolic localization is supported by experimental evidence. PMID:30642431 demonstrates that SUMOylated DVE-1 localizes to the cytosol, and desumoylation by ULP-4 is required for nuclear accumulation during mitochondrial stress. UniProt notes that DVE-1 translocates from cytosol to nucleus upon mitochondrial stress. Supporting Evidence: PMID:30642431 Conversely, SUMO-mimetic DVE-1 constitutively localized in the cytosol (Figure 3G) |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000002 | ACCEPT | Summary: DVE-1 participates in chromatin remodeling via interaction with NuRD complex and HDA-1. Reason: This IEA annotation (from InterPro) is consistent with DVE-1's SATB-like domain structure and experimental evidence. DVE-1 associates with the NuRD chromatin remodeling complex (PMID:32789178) and cooperates with HDA-1 (PMID:32934238) to regulate chromatin state. Duplicate with IBA annotation above but both are acceptable given different evidence sources. Supporting Evidence: PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: DVE-1 regulates RNA polymerase II-dependent transcription of many genes. Reason: This IEA annotation is accurate. DVE-1 regulates transcription of UPR-mt target genes and thousands of additional genes. This is a duplicate of the IBA annotation but from a different evidence source. Both are acceptable. Supporting Evidence: PMID:17925224 Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000108 | ACCEPT | Summary: DVE-1 positively regulates transcription of UPR-mt target genes including hsp-6, hsp-60, and nhr-80. Reason: This annotation is well-supported. DVE-1 functions as a transcriptional activator for mitochondrial chaperone genes during UPR-mt (PMID:17925224) and for nhr-80 in lipid metabolism (PMID:35021096). The IDA annotation for GO:0001228 (DNA-binding transcription activator activity) provides direct experimental support for this role. Supporting Evidence: PMID:35021096 The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:35021096 NHR-80 senses the mitochondrial UPR to rewire citrate metabo... | ACCEPT | Summary: DVE-1 functions as a transcriptional activator, directly binding to the nhr-80 promoter and transactivating its expression in response to citrate-induced UPR-mt. Reason: This IDA annotation from PMID:35021096 is directly supported by experimental evidence showing DVE-1 binds to and transactivates the nhr-80 promoter. The study demonstrates the DVE-1-NHR-80-lipogenesis axis linking mitochondrial stress to lipid metabolism. Inactivation of DVE-1 abolishes citrate-induced lipid accumulation. Supporting Evidence: PMID:35021096 The transcription factor DVE-1 binds to the promoter of the nuclear hormone receptor nhr-80 to transactivate its expression |
| GO:0045088 regulation of innate immune response | IMP PMID:32934238 Histone deacetylase HDA-1 modulates mitochondrial stress res... | ACCEPT | Summary: DVE-1 is required for UPR-mt-mediated innate immune responses, including survival against pathogen challenge. Reason: PMID:32934238 demonstrates that dve-1 RNAi suppresses activation of immune response genes and reduces survival when animals are challenged with pathogens (Pseudomonas, Rhodococcus) under mitochondrial stress conditions. DVE-1 cooperates with HDA-1 to induce transcription of innate immune response genes. Supporting Evidence: PMID:32934238 hda-1 or dve-1 RNAi also suppressed the activation of the immune response and reduced the survival rate when the animals were challenged with another mitochondrial insult, a Rhodococcus strain isolated from the natural habitat of C. elegans |
| GO:0000785 chromatin | IDA PMID:32934238 Histone deacetylase HDA-1 modulates mitochondrial stress res... | ACCEPT | Summary: DVE-1 associates with chromatin where it functions as a genome organizer coordinating with HDA-1 and the NuRD complex. Reason: PMID:32934238 describes DVE-1 as a "genome organizer" that coordinates with HDA-1 at chromatin to regulate gene expression. PMID:32789178 shows DVE-1 associates with the NuRD complex. DVE-1 binds to promoter chromatin of target genes. The SATB family homology further supports chromatin association. Supporting Evidence: PMID:32934238 HDA-1 interacts and coordinates with the genome organizer DVE-1 to induce the transcription of a broad spectrum of UPRmt, innate immune response and metabolic reprogramming genes |
| GO:0005634 nucleus | IDA PMID:32934238 Histone deacetylase HDA-1 modulates mitochondrial stress res... | ACCEPT | Summary: DVE-1::GFP accumulates in the nucleus under mitochondrial stress conditions. Reason: PMID:32934238 uses DVE-1::GFP reporter to demonstrate nuclear localization. Multiple other publications (PMID:17925224, PMID:30642431, PMID:32789178) confirm nuclear localization of DVE-1 during mitochondrial stress using similar approaches. Supporting Evidence: PMID:32934238 HDA-1 interacts and coordinates with the genome organizer DVE-1 to induce the transcription of a broad spectrum of UPRmt, innate immune response and metabolic reprogramming genes |
| GO:0019899 enzyme binding | IPI PMID:30642431 SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated in... | ACCEPT | Summary: DVE-1 interacts with the SUMO peptidase ULP-4, which desumoylates DVE-1 at K327 to allow nuclear accumulation during UPR-mt. Reason: DVE-1 interacts with ULP-4 (PMID:30642431), a SUMO peptidase enzyme. ULP-4 is an enzyme and DVE-1 is its substrate, so enzyme binding accurately describes this interaction. The interaction is functionally important for regulating DVE-1 localization during mitochondrial stress. Supporting Evidence: PMID:30642431 DVE-1 interacts with ULP-4 and SMO-1 in yeast two-hybrid assay |
| GO:0019899 enzyme binding | IPI PMID:32934238 Histone deacetylase HDA-1 modulates mitochondrial stress res... | ACCEPT | Summary: DVE-1 interacts with HDA-1 (histone deacetylase), an enzyme that modifies chromatin. Reason: PMID:32934238 demonstrates that DVE-1 interacts with HDA-1, the C. elegans ortholog of mammalian HDAC1/2. HDA-1 is a histone deacetylase enzyme. The interaction coordinates chromatin regulation for UPR-mt gene expression. "Enzyme binding" accurately describes this interaction. Supporting Evidence: PMID:32934238 HDA-1 interacts and coordinates with the genome organizer DVE-1 to induce the transcription of a broad spectrum of UPRmt, innate immune response and metabolic reprogramming genes |
| GO:0034514 mitochondrial unfolded protein response | IMP PMID:30642431 SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated in... | ACCEPT | Summary: DVE-1 is essential for the mitochondrial unfolded protein response. SUMOylation regulates DVE-1 localization during UPR-mt activation. Reason: PMID:30642431 demonstrates that ULP-4-mediated desumoylation of DVE-1 is required for UPR-mt activation. DVE-1 is one of two key transcription factors (along with ATFS-1) governing the UPR-mt transcriptional program. dve-1 RNAi attenuates hsp-6/hsp-60 reporter induction. Supporting Evidence: PMID:30642431 during mitochondrial stress, ULP-4 deSUMOylates DVE-1 at K327 residue to allow its nuclear accumulation to initiate UPRmt |
| GO:0044877 protein-containing complex binding | IDA PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chr... | ACCEPT | Summary: DVE-1 associates with the NuRD (Nucleosome Remodeling and Deacetylase) complex via interaction with LIN-40. Reason: PMID:32789178 demonstrates DVE-1 interacts with LIN-40 and associates with the NuRD complex. This interaction mediates chromatin remodeling in response to mitochondrial stress and acetyl-CoA levels. The annotation accurately reflects DVE-1's binding to this multi-protein complex. Supporting Evidence: PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level |
| GO:0005515 protein binding | IPI PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chr... | MARK AS OVER ANNOTATED | Summary: DVE-1 interacts with LIN-40, a component of the NuRD complex. Reason: While DVE-1 does interact with LIN-40 (PMID:32789178), "protein binding" is too generic and uninformative. The more specific annotation GO:0044877 "protein-containing complex binding" from the same publication better captures this interaction. GO guidelines recommend avoiding generic "protein binding" when more specific terms apply. Supporting Evidence: PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level |
| GO:0005634 nucleus | IDA PMID:30642431 SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated in... | ACCEPT | Summary: DVE-1 localizes to nucleus upon mitochondrial stress after desumoylation by ULP-4. Reason: PMID:30642431 uses DVE-1::GFP imaging to demonstrate nuclear localization. The study shows that desumoylation at K327 is required for nuclear accumulation during mitochondrial stress. DVE-1 K327R (non-SUMOylatable) constitutively localizes to the nucleus. Supporting Evidence: PMID:30642431 DVE-1 K327R constitutively localized in the nucleus of C. elegans, even if ulp-4 was knocked down by RNAi (Figure 3F) |
| GO:0005634 nucleus | IDA PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chr... | ACCEPT | Summary: DVE-1::GFP shows nuclear localization in response to mitochondrial stress. Reason: PMID:32789178 demonstrates nuclear accumulation of DVE-1::GFP under mitochondrial stress conditions using fluorescence microscopy. This is consistent with other publications. Duplicate annotations with different references are acceptable. Supporting Evidence: PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level |
| GO:0005829 cytosol | IDA PMID:30642431 SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated in... | ACCEPT | Summary: SUMOylated DVE-1 localizes to the cytosol. Desumoylation by ULP-4 allows nuclear translocation. Reason: PMID:30642431 directly demonstrates that SUMOylation at K327 retains DVE-1 in the cytosol. A SUMO-mimetic DVE-1 fusion constitutively localizes to the cytosol. This provides direct evidence for cytosolic localization under specific conditions. Supporting Evidence: PMID:30642431 Conversely, SUMO-mimetic DVE-1 constitutively localized in the cytosol (Figure 3G) |
| GO:0005829 cytosol | IDA PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chr... | ACCEPT | Summary: DVE-1 can be found in the cytosol, consistent with its stress-induced translocation from cytosol to nucleus. Reason: PMID:32789178 studies DVE-1::GFP localization dynamics. The cytosolic pool of DVE-1 translocates to nucleus upon mitochondrial stress. UniProt annotates cytosol based on this evidence. Supporting Evidence: PMID:32789178 NuRD mediates mitochondrial stress-induced longevity via chromatin remodeling in response to acetyl-CoA level |
| GO:0034514 mitochondrial unfolded protein response | IMP PMID:30057120 The Mitochondrial Unfolded Protein Response Is Mediated Cell... | ACCEPT | Summary: DVE-1 functions in cell-non-autonomous UPR-mt signaling mediated by Wnt signaling. Reason: PMID:30057120 examines cell-non-autonomous UPR-mt signaling via Wnt pathway. DVE-1 is a known component of the UPR-mt transcriptional program activated downstream of this signaling. The publication expands understanding of how UPR-mt is coordinated across tissues. Supporting Evidence: PMID:30057120 The mitochondrial unfolded protein response (UPRmt) can be triggered in a cell-non-autonomous fashion |
| GO:0034514 mitochondrial unfolded protein response | IMP PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein... | ACCEPT | Summary: DVE-1 was identified as a key regulator of UPR-mt in the foundational genome-wide RNAi screen. Required for activation of mitochondrial chaperone gene expression. Reason: PMID:17925224 is the seminal publication identifying DVE-1's role in UPR-mt. A genome-wide RNAi screen identified dve-1 as required for UPR-mt signaling. DVE-1 forms a complex with UBL-5, redistributes to nucleus, and binds to promoters of mitochondrial chaperone genes under stress. Supporting Evidence: PMID:17925224 Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5, both of which are encoded by genes required for signaling the UPR(mt) |
| GO:0005667 transcription regulator complex | IPI PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein... | ACCEPT | Summary: DVE-1 forms a complex with UBL-5 to regulate UPR-mt gene transcription. This complex forms specifically under mitochondrial stress conditions. Reason: PMID:17925224 demonstrates that DVE-1 and UBL-5 form a complex in a mitochondrial stress-dependent manner. This DVE-1/UBL-5 complex is required for transcriptional regulation of UPR-mt target genes. UniProt confirms the interaction. Supporting Evidence: PMID:17925224 Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5 |
| GO:0051087 protein-folding chaperone binding | IPI PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein... | UNDECIDED | Summary: WormBase IPI annotation with WITH/FROM WB:WBGene00002025 (hsp-60), asserting that DVE-1 binds the mitochondrial chaperonin HSP-60. It is the mirror of the hsp-60 row enables GO:0061629 (IPI, WITH dve-1) from the same paper; the DVE-1/UBL-5 complex is recorded separately as GO:0005667 (IPI, WITH UniProtKB:P91302). Reason: The partner is HSP-60, a bona fide protein-folding chaperone, so the term fits the partner. The cached record for PMID:17925224 is abstract-only and does not describe an HSP-60/DVE-1 interaction, so the assay behind it cannot be checked; the curator read the full text, so the row is not removed. The open question is which assay established the interaction and how a mitochondrial matrix chaperonin contacts a nuclear homeodomain factor. The quoted abstract sentence is context (the DVE-1/UBL-5 complex), not direct support for HSP-60 binding. Supporting Evidence: PMID:17925224 Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5 |
| GO:0005634 nucleus | IDA PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein... | ACCEPT | Summary: DVE-1 redistributes to the nucleus under mitochondrial stress, as shown by the foundational UPR-mt study. Reason: PMID:17925224 demonstrates nuclear redistribution of DVE-1 correlates with UPR-mt activation. This is the original publication establishing DVE-1 nuclear localization during mitochondrial stress. Supporting Evidence: PMID:17925224 Activation of the UPR(mt) correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes |
| GO:0009792 embryo development ending in birth or egg hatching | IMP PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein... | KEEP AS NON CORE | Summary: DVE-1 is essential for embryonic development. Null alleles are embryonic lethal. Reason: PMID:17925224 and UniProt note that dve-1 is required for embryonic development (null alleles are lethal). However, this is likely a consequence of DVE-1's essential role in transcriptional regulation and chromatin organization rather than a specific developmental function. The core function is as a UPR-mt transcriptional regulator and chromatin organizer. Supporting Evidence: file:worm/dve-1/dve-1-deep-research-falcon.md DVE-1 is required for embryonic development PMID:17925224 ClpP mediates activation of a mitochondrial unfolded protein response in C. |
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Download this section (compressed HTML)Q: Does DVE-1 have direct repressor activity for certain gene sets, or is it primarily an activator?
Q: What is the DNA binding motif/consensus sequence for DVE-1 target sites?
Q: How do the two homeobox domains cooperate in DNA binding and target selection?
Q: What determines the context-dependent switch between DVE-1 activator and repressor functions?
Experiment: ChIP-seq for DVE-1 to comprehensively map genomic binding sites and identify consensus motif.
Hypothesis: DVE-1 binds to a specific DNA motif at promoters of UPR-mt target genes.
Experiment: Structure-function analysis of individual homeobox domains to determine their contributions.
Hypothesis: The two homeobox domains have distinct or cooperative roles in DNA binding.
Experiment: Time-resolved proteomics of DVE-1 complexes under different stress conditions.
Hypothesis: DVE-1 forms distinct protein complexes under different physiological conditions.
Experiment: Single-cell analysis of DVE-1 activity across tissues during UPR-mt.
Hypothesis: DVE-1 activation varies across cell types during systemic mitochondrial stress.
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