hairy (h) is a basic helix-loop-helix-Orange (bHLH-O), HES-family sequence-specific DNA-binding transcriptional repressor of Drosophila melanogaster. Through a repressor-type bHLH domain bearing a helix-interrupting proline it binds N-box (CACNAG) and related class-C/E-box sites in target promoters, and it represses transcription by recruiting the Groucho (Gro/TLE) corepressor through its C-terminal WRPW tetrapeptide, with an accessory, weaker interaction with the CtBP corepressor. Hairy is a primary pair-rule segmentation gene that patterns the anterior-posterior axis of the early embryo, repressing targets such as fushi tarazu, and it also patterns the adult peripheral nervous system, setting sensory bristle (chaeta) spacing by directly repressing the proneural achaete-scute genes. It acts in the nucleus and functions as a long-range transcriptional repressor. Its repressive activity is modulated post-translationally by RING/SUMO-targeted ubiquitin ligases (Topors, Degringolade) that bind Hairy and antagonize Groucho recruitment or trigger its degradation. Additional context-dependent roles include repression of metabolic genes contributing to hypoxia tolerance and, indirectly through its target genes, effects on epithelial tube (e.g. salivary gland) morphogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) annotation of Hairy as a negative regulator of Pol II transcription. This is the central, well-supported function of Hairy as a bHLH-O repressor. Reason: Directly supported by experimental data showing Hairy is a transcriptional repressor of achaete and ftz, acting via Groucho recruitment. The IBA sits at an appropriate level of specificity for a HES-family repressor. Supporting Evidence: PMID:7958929 transcriptional repressor |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic assignment of sequence-specific Pol II transcription factor activity. Correct at the family level; Hairy is more precisely a repressor (GO:0001227, separately annotated by IDA). Reason: Hairy is a sequence-specific Pol II DNA-binding transcription factor. The parent term is accurate; the repressor-specific child GO:0001227 captured elsewhere in this set gives the finer specificity, so this general IBA is retained rather than modified. Supporting Evidence: PMID:7958929 DNA-binding protein and transcriptional repressor |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic localization to the nucleus, consistent with Hairy being a nuclear DNA-binding transcriptional repressor. Reason: Hairy is a sequence-specific DNA-binding transcription factor and acts in the nucleus; UniProt records nuclear localization and the term is corroborated by IEA and IC annotations in this set. |
| GO:0009952 anterior/posterior pattern specification | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation reflecting Hairy's role as a pair-rule gene patterning the anterior-posterior body axis of the embryo. Reason: Hairy is a primary pair-rule segmentation gene; A/P pattern specification is an accurate parent process for its segmentation role. Supporting Evidence: PMID:9524128 hairy is a Drosophila pair-rule segmentation gene that functions genetically as |
| GO:0050767 regulation of neurogenesis | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation reflecting Hairy's role in the peripheral nervous system, where it regulates sensory organ precursor selection by repressing proneural genes. Reason: Directly supported experimentally: Hairy represses the proneural gene achaete, controlling adult bristle (sensory organ) patterning. Supporting Evidence: PMID:7958929 direct downstream target of h regulation in vivo |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of sequence-specific binding to Pol II cis-regulatory regions, matching Hairy's direct binding of target promoters/enhancers. Reason: Hairy binds specific sites (N-box/class-C sites) in target cis-regulatory regions; corroborated by IDA from PMID:7958929. Supporting Evidence: PMID:7958929 DNA-binding protein and transcriptional repressor |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation of generic DNA binding, consistent with the bHLH DNA-binding domain. Reason: Broad but correct; Hairy is a demonstrated sequence-specific DNA-binding protein. A more informative sequence-specific child term is separately annotated. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location electronic annotation to the nucleus. Reason: Consistent with Hairy's function as a nuclear DNA-binding transcriptional repressor and with the IBA/IC nucleus annotations. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic annotation of transcriptional regulation, a broad parent of Hairy's repressor activity. Reason: Correct but general; Hairy is specifically a negative regulator (repressor), captured by more specific terms in this set. The broad IEA is retained as acceptable. |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro electronic annotation of dimerization activity, inferred from the bHLH domain that mediates helix-loop-helix dimerization. Reason: Defensible at the family level (bHLH-O proteins dimerize via the HLH domain). Note that Hairy does not promiscuously heterodimerize with class I/II bHLH proteins (PMID:9371806 reports Hairy displays no interactions with any of the HLH proteins tested), so the activity is best understood as homodimerization/family-level rather than broad bHLH heterodimerization; the broad IEA is retained. |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning electronic annotation of sequence-specific double-stranded DNA binding. Reason: Consistent with experimentally demonstrated sequence-specific DNA binding by Hairy (PMID:7958929). Supporting Evidence: PMID:7958929 DNA-binding protein and transcriptional repressor |
| GO:0005515 protein binding | IPI PMID:14871887 Drosophila Topors is a RING finger-containing protein that f... | MODIFY | Summary: IPI annotation from the Topors study. The interacting partner, dTopors, is a RING-finger ubiquitin-protein ligase that binds the basic region of Hairy and mediates its polyubiquitination. Reason: Bare protein binding is uninformative. The identified partner is the E3 ubiquitin ligase Topors, so ubiquitin protein ligase binding is the informative molecular function. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:14871887 binds specifically to the basic region of Hairy PMID:14871887 dTopors mediates Hairy polyubiquitination |
| GO:0005515 protein binding | IPI PMID:16455680 Physical and genetic interactions link hox function with div... | MODIFY | Summary: IPI from a Hox interactome screen showing a physical interaction between Hairy and the Hox protein Ultrabithorax (UBX). Reason: Bare protein binding is uninformative, and the partner is curated input data: the GOA row carries WITH/FROM = UniProtKB:P83949, resolved by the fetched UniProt record as Ubx (hairy-uniprot.txt:131, 'P14003; P83949: Ubx'). Ultrabithorax is a Hox homeodomain sequence-specific DNA-binding transcription factor, so GO:0140297 DNA-binding transcription factor binding is the informative term - the same WITH/FROM-driven treatment applied to every other GO:0005515 IPI row in this file (GO:0031625 for the Topors and Degringolade rows, GO:0001222 for the Groucho and CtBP rows). The interaction is peripheral and context-specific rather than part of Hairy's core repressor mechanism, so it should not be treated as a core function, but that belongs in the reason rather than in retaining a bare uninformative term. Proposed replacements: DNA-binding transcription factor binding Supporting Evidence: PMID:16455680 Interactions were confirmed with wild-type Ultrabithorax (UBX) in phage display PMID:16455680 pupal death phenotype induced by ectopic expression of the UBX partner Hairy |
| GO:0005515 protein binding | IPI PMID:17898168 A Myc-Groucho complex integrates EGF and Notch signaling to ... | MODIFY | Summary: IPI from the dMyc-Groucho study; the curated partner is Groucho (isoform 2). Reason: Bare protein binding is uninformative, and the partner is not unverifiable: the GOA row carries WITH/FROM = UniProtKB:P16371-2, resolved by the fetched UniProt record as Groucho isoform 2 (hairy-uniprot.txt:129, 'P14003; P16371-2: gro'). The cached record is abstract-only, but partner identity is curated input data rather than something that has to be recovered from the abstract, so the unverifiable-evidence policy does not apply. Groucho is a transcriptional corepressor and Hairy-Groucho recruitment via the WRPW motif is this protein's canonical repression mechanism, already captured at GO:0001222 on the PMID:10433905, PMID:8649374, PMID:9371806 and PMID:9892668 rows; assign the same term here for consistency. Proposed replacements: transcription corepressor binding Supporting Evidence: UniProtKB:P14003 Interacts with gro (via WPRW motif) |
| GO:0005515 protein binding | IPI PMID:19805071 Groucho corepressor functions as a cofactor for the Knirps s... | MODIFY | Summary: IPI from the Knirps-Groucho short-range repression study; the curated partner for the Hairy row is Groucho. Reason: Bare protein binding is uninformative, and the partner underlying this IPI is stated rather than unconfirmable: the GOA row carries WITH/FROM = UniProtKB:P16371, resolved by the fetched UniProt record as Groucho (hairy-uniprot.txt:128, 'P14003; P16371: gro'). Although the paper's headline result concerns Knirps, curated partner identity is input data, not an inference from the text, and Hairy-Groucho is the canonical WRPW-motif corepressor interaction annotated at GO:0001222 elsewhere in this file. Assign transcription corepressor binding. Proposed replacements: transcription corepressor binding Supporting Evidence: UniProtKB:P14003 Interacts with gro (via WPRW motif) |
| GO:0005515 protein binding | IPI PMID:21343912 Degringolade, a SUMO-targeted ubiquitin ligase, inhibits Hai... | MODIFY | Summary: IPI from the Degringolade (Dgrn) study. Dgrn is a RING-finger/SUMO-targeted ubiquitin ligase that binds and ubiquitinates Hairy to inhibit Groucho recruitment. This stub collapses three GOA rows from this reference, whose WITH/FROM accessions are UniProtKB:Q9VNJ0 (dgrn), UniProtKB:O46036 (CtBP) and UniProtKB:P16371 (gro). Reason: Bare protein binding is uninformative. Of the three partners this reference contributes, Degringolade is an E3 ubiquitin ligase, so ubiquitin protein ligase binding is the informative molecular function for that row; CtBP and Groucho are transcriptional corepressors, so transcription corepressor binding is needed alongside it to cover the other two rows (all three accessions read off the GOA WITH/FROM column and confirmed against hairy-uniprot.txt:126-128). Proposed replacements: ubiquitin protein ligase binding transcription corepressor binding Supporting Evidence: PMID:21343912 Dgrn is a negative regulator of the repressor Hairy and its corepressor Groucho PMID:21343912 it targets Hairy for SUMO-independent ubiquitylation that inhibits the recruitment of its corepressor Gro |
| GO:0005515 protein binding | IPI PMID:9371806 A network of interacting transcriptional regulators involved... | MODIFY | Summary: Yeast two-hybrid neural-fate network study directly demonstrating that Hairy interacts with the corepressor Groucho (and not with the tested proneural/E(spl)/Da bHLH proteins). Reason: Bare protein binding is uninformative. The demonstrated partner is the transcriptional corepressor Groucho, so transcription corepressor binding is the informative MF. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:9371806 It does interact with the non-HLH protein Groucho |
| GO:0005515 protein binding | IPI PMID:9524128 Drosophila CtBP: a Hairy-interacting protein required for em... | MODIFY | Summary: IPI identifying dCtBP as a direct Hairy-interacting protein binding a small C-terminal region of Hairy and required for Hairy-mediated repression and embryonic segmentation. Reason: Bare protein binding is uninformative. The partner CtBP is a transcriptional corepressor, so transcription corepressor binding is the informative MF. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:9524128 dCtBP interacts |
| GO:0005515 protein binding | IPI PMID:9892668 Groucho and dCtBP mediate separate pathways of transcription... | MODIFY | Summary: IPI from the Groucho/dCtBP repression-pathway study; Hairy is one of the long-range repressors that recruit the Groucho corepressor. Reason: Bare protein binding is uninformative. The functionally dominant partner is the Groucho corepressor, so transcription corepressor binding is the informative MF. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:9892668 the two long-range repressors, Hairy and Dorsal, recruit a different corepressor |
| GO:0001222 transcription corepressor binding | IPI PMID:10433905 Huckebein repressor activity in Drosophila terminal patterni... | ACCEPT | Summary: Transcription corepressor binding, reflecting Hairy's recruitment of Groucho through its WRPW motif (the Huckebein study establishes the shared WRPW/FRPW Groucho-recruitment paradigm for Hairy-related repressors). Reason: This is an informative molecular function capturing the core repression mechanism (Groucho recruitment). Retained as a key MF; corroborated by direct Hairy-Groucho interaction data (PMID:9371806, PMID:8649374). Supporting Evidence: PMID:10433905 WRPW Groucho-recruitment domain found in |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:25569482 Origins of context-dependent gene repression by capicua. | ACCEPT | Summary: Experimental annotation in which Hairy is used as a WRPW/Groucho-dependent repressor; expression of Hairy represses the Sxl target in embryos. Reason: Consistent with Hairy's core function as a negative regulator of Pol II transcription; the study assays Hairy-mediated, WRPW-dependent repression in vivo. Supporting Evidence: PMID:25569482 used to replace the Gro-binding WRPW motif of the Hairy repressor and tested for its ability to repress Sxl expression in the embryo PMID:25569482 Repression depends on the WRPW motif of Hairy |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:7958929 Negative regulation of proneural gene activity: hairy is a d... | ACCEPT | Summary: Direct demonstration that Hairy is a transcriptional repressor, repressing the proneural gene achaete in vivo. Core function. Reason: One of the defining experimental results for Hairy: it is a sequence-specific DNA-binding transcriptional repressor of a Pol II target gene. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:7958929 Negative regulation of proneural gene activity: hairy is a d... | ACCEPT | Summary: Direct demonstration that Hairy is a sequence-specific DNA-binding protein recognizing a defined high-affinity site in the achaete cis-regulatory region. Reason: Core DNA-binding function; a single conserved high-affinity Hairy site upstream of achaete is required for repression in vivo. Supporting Evidence: PMID:7958929 direct downstream target of h regulation in vivo |
| GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific | IDA PMID:7958929 Negative regulation of proneural gene activity: hairy is a d... | ACCEPT | Summary: Direct experimental annotation of Hairy as a sequence-specific DNA-binding Pol II transcriptional repressor. This is the most informative molecular-function term for Hairy. Reason: Precisely captures Hairy's core molecular function as an active, sequence-specific DNA-binding repressor of Pol II transcription. Supporting Evidence: PMID:7958929 DNA-binding protein and transcriptional repressor PMID:7958929 transcriptional repressor |
| GO:0070888 E-box binding | IDA PMID:7958929 Negative regulation of proneural gene activity: hairy is a d... | ACCEPT | Summary: FlyBase IDA of E-box binding. Hairy binds a defined high-affinity site in the achaete regulatory region; the Hairy-class recognition site is a class-C/N-box-type element. Reason: Retained as an experimental (IDA) binding-specificity annotation, deferring to the curator who read the full text. Note that UniProt records a preference of Hairy's proline-interrupted basic region for the N-box (CACNAG) over the canonical E-box (CANNTG); the E-box and N-box/class-C annotations both reflect genuine sequence-specific binding and are not contradictory. Supporting Evidence: PMID:7958929 DNA-binding protein and transcriptional repressor |
| GO:0000902 cell morphogenesis | IMP PMID:12526813 Epithelial tube morphology is determined by the polarized gr... | KEEP AS NON CORE | Summary: IMP from a new hairy allele causing salivary tube shape defects. The effect is indirect, mediated by failure to repress huckebein. Reason: Genuine mutant phenotype but a downstream morphogenetic consequence of loss of Hairy's transcriptional repression (via prolonged huckebein expression), not a distinct core function of this nuclear repressor. Retained as non-core. Supporting Evidence: PMID:12526813 hairy mutations cause branching and bulging of the normally PMID:12526813 prolonged expression of huckebein |
| GO:0007435 salivary gland morphogenesis | IMP PMID:12526813 Epithelial tube morphology is determined by the polarized gr... | KEEP AS NON CORE | Summary: IMP: hairy mutations cause branching/bulging of the salivary tube via prolonged huckebein expression. Reason: Pleiotropic developmental role that is an indirect consequence of loss of Hairy-mediated repression of huckebein; retained as non-core rather than a core function. Supporting Evidence: PMID:12526813 hairy mutations cause branching and bulging of the normally |
| GO:0007435 salivary gland morphogenesis | IGI PMID:12526813 Epithelial tube morphology is determined by the polarized gr... | KEEP AS NON CORE | Summary: Genetic-interaction evidence (IGI) for the same salivary-gland role, consistent with the hairy-huckebein-crumbs/klarsicht regulatory relationships described in the study. Reason: Corroborates the salivary gland role via genetic interactions; still an indirect, pleiotropic developmental role and retained as non-core. Supporting Evidence: PMID:12526813 prolonged expression of huckebein |
| GO:0035239 tube morphogenesis | IMP PMID:12526813 Epithelial tube morphology is determined by the polarized gr... | KEEP AS NON CORE | Summary: IMP for the broader tube-morphogenesis process, reflecting the salivary tube shape defects of hairy mutants. Reason: Broader parent of the salivary-gland phenotype; an indirect consequence of loss of Hairy repression and retained as non-core. Supporting Evidence: PMID:12526813 hairy mutations cause branching and bulging of the normally |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:7768186 Pair-rule expression of the Drosophila fushi tarazu gene: a ... | ACCEPT | Summary: Direct evidence that Hairy represses the pair-rule gene fushi tarazu (ftz) through a defined fDE1 element during blastoderm segmentation. Reason: Supports Hairy's core repressor function in embryonic segmentation; ftz reporter expression depends on activation by runt and repression by hairy. Supporting Evidence: PMID:7768186 runt and hairy are required for the proper PMID:7768186 repression by hairy |
| GO:0001666 response to hypoxia | IMP PMID:18927626 Mechanisms underlying hypoxia tolerance in Drosophila melano... | KEEP AS NON CORE | Summary: IMP from hypoxia-tolerance selection experiments; hairy is up-regulated in tolerant flies and acts as a metabolic switch repressing metabolic genes, and hairy mutations reduce hypoxia tolerance. Reason: Genuine but context-specific, pleiotropic role in which Hairy's repressor activity is deployed on metabolic target genes; retained as a non-core biological process. Supporting Evidence: PMID:18927626 The transcriptional suppressor, hairy, was up-regulated PMID:18927626 hairy acting as a metabolic switch |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:8649374 The WRPW motif of the hairy-related basic helix-loop-helix r... | ACCEPT | Summary: Direct demonstration that Hairy-related repressors actively repress transcription via the WRPW motif recruiting Groucho/TLE corepressors to target promoters. Reason: Core repressor function; the WRPW motif is shown to be a sufficient active repression domain that recruits Groucho. Supporting Evidence: PMID:8649374 recruited by the 4-amino acid protein-protein interaction domain, WRPW |
| GO:0003677 DNA binding | IDA PMID:8649374 The WRPW motif of the hairy-related basic helix-loop-helix r... | ACCEPT | Summary: DNA binding annotation; Hairy-related proteins are defined as site-specific DNA-binding proteins with a repressor-specific bHLH domain. Reason: Consistent with Hairy's demonstrated sequence-specific DNA binding; broad but correct. Supporting Evidence: PMID:8649374 presence of both a repressor-specific bHLH DNA binding domain and a |
| GO:0005515 protein binding | IPI PMID:8649374 The WRPW motif of the hairy-related basic helix-loop-helix r... | MODIFY | Summary: IPI reflecting the Hairy-Groucho interaction mediated by the WRPW motif, shown to recruit Groucho/TLE corepressors to promoters. Reason: Bare protein binding is uninformative. The partner recruited by the WRPW motif is the Groucho corepressor, so transcription corepressor binding is the informative MF. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:8649374 recruited by the 4-amino acid protein-protein interaction domain, WRPW |
| GO:0005634 nucleus | IC PMID:8649374 The WRPW motif of the hairy-related basic helix-loop-helix r... | ACCEPT | Summary: Curator-inferred (IC) nuclear localization, consistent with Hairy acting as a promoter-bound DNA-binding repressor that recruits Groucho. Reason: Consistent with Hairy's nuclear DNA-binding transcriptional-repressor function and other nucleus annotations in this set. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:8649374 The WRPW motif of the hairy-related basic helix-loop-helix r... | ACCEPT | Summary: Direct evidence of active transcriptional repression by Hairy-related proteins via the WRPW/Groucho mechanism. Reason: Supports the core repressor function at the DNA-templated-transcription level; WRPW is a sufficient active repression domain. Supporting Evidence: PMID:8649374 recruited by the 4-amino acid protein-protein interaction domain, WRPW |
| GO:0007424 open tracheal system development | IMP PMID:15848387 A molecular link between FGF and Dpp signaling in branch-spe... | UNDECIDED | Summary: IMP for a role in tracheal development. The cited paper is an EMS tracheal mutagenesis screen; the cached full text (available) foregrounds btl, pointed, and kni/knrl and does not mention hairy. Reason: The supporting evidence for a hairy tracheal role cannot be verified from the cached full text (zero occurrences of the gene name), and the specific complementation group is not named in the available text. Following curation policy for unverifiable experimental annotations, this is marked UNDECIDED rather than accepted or removed. |
| GO:0061024 membrane organization | TAS PMID:12593813 Tube morphogenesis: no pipe dream in Drosophila. | MARK AS OVER ANNOTATED | Summary: TAS annotation traced to a Current Biology dispatch on tubular-organ lumen size and intracellular vesicle transport. Reason: Hairy is a sequence-specific nuclear transcriptional repressor; membrane organization is a distal phenotypic consequence (apical-membrane growth during salivary tube morphogenesis, itself downstream of huckebein derepression) rather than a molecular or cellular function of Hairy. The reference is a review dispatch that does not describe a Hairy function. Flagged as an over-annotation. |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IMP PMID:9892668 Groucho and dCtBP mediate separate pathways of transcription... | ACCEPT | Summary: IMP from transgenic misexpression of wild-type and mutant Hairy showing that Hairy-mediated repression in the embryo depends on the WRPW/Groucho interaction. Reason: Supports the core repressor function; Hairy repression in vivo requires the Groucho-recruitment (WRPW) sequence. Supporting Evidence: PMID:9892668 Hairy-mediated |
| GO:0000122 negative regulation of transcription by RNA polymerase II | IPI PMID:9892668 Groucho and dCtBP mediate separate pathways of transcription... | ACCEPT | Summary: Annotation linking Hairy's negative regulation of transcription to its physical recruitment of the Groucho corepressor (the two long-range repressors Hairy and Dorsal recruit Groucho). Reason: Consistent with the core repressor function; Hairy-mediated repression is Groucho-dependent. Supporting Evidence: PMID:9892668 the two long-range repressors, Hairy and Dorsal, recruit a different corepressor |
| GO:0007366 periodic partitioning by pair rule gene | TAS PMID:10611687 The origin and evolution of segmentation. | ACCEPT | Summary: TAS annotation of Hairy's canonical role as a pair-rule gene contributing to periodic (segmental) partitioning of the embryo. Reason: Hairy is a primary pair-rule segmentation gene; periodic partitioning by pair-rule gene is a precise, core segmentation process. Supported by primary literature establishing Hairy as a pair-rule repressor. Supporting Evidence: PMID:9524128 hairy is a Drosophila pair-rule segmentation gene that functions genetically as |
| GO:0007366 periodic partitioning by pair rule gene | TAS PMID:15382142 The evolution of arthropod segmentation mechanisms. | ACCEPT | Summary: TAS annotation (arthropod-segmentation review) placing Hairy among the primary pair-rule genes contributing to periodic segmental partitioning. Reason: Core segmentation role, consistent with Hairy being one of the primary pair-rule genes of Drosophila. Supporting Evidence: PMID:15382142 primary pair-rule genes of Drosophila |
| GO:0007399 nervous system development | TAS PMID:12815726 The role of class I HLH genes in neural development--have th... | KEEP AS NON CORE | Summary: Broad TAS annotation of nervous system development, traced to a review of HLH gene classes in neural development. Reason: Hairy does function in nervous-system (bristle/SOP) patterning via repression of proneural genes, so the broad term is not wrong; however it is a very general parent captured more precisely by regulation of neurogenesis, and the cited reference is a generic HLH-class review rather than a Hairy study. Retained as non-core. Supporting Evidence: PMID:7958929 negative regulator in both embryonic segmentation and adult |
| GO:0035289 posterior head segmentation | TAS PMID:15382142 The evolution of arthropod segmentation mechanisms. | ACCEPT | Summary: TAS annotation of a role in posterior head segmentation, within Hairy's pair-rule segmentation function. Reason: Consistent with Hairy's pair-rule segmentation role; retained as part of the core segmentation function. Supporting Evidence: PMID:15382142 primary pair-rule genes of Drosophila |
| GO:0035290 trunk segmentation | TAS PMID:15382142 The evolution of arthropod segmentation mechanisms. | ACCEPT | Summary: TAS annotation of trunk segmentation, the principal segmental domain patterned by the pair-rule gene Hairy. Reason: Core segmentation process; Hairy is a primary pair-rule gene patterning the trunk. Supporting Evidence: PMID:15382142 primary pair-rule genes of Drosophila |
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Download this section (compressed HTML)Q: To what extent does Hairy repress through the N-box (CACNAG) versus E-box/class-C sites genome-wide, and does binding-site type correlate with distinct target-gene classes (segmentation vs. proneural vs. metabolic)?
Q: How is the balance between Groucho- and CtBP-dependent repression by Hairy set at individual target loci, given the evidence that the two corepressors act through separate, sometimes antagonistic, pathways?
Experiment: Genome-wide binding (CUT&RUN or ChIP-seq) of Hairy in staged embryos combined with motif analysis to quantify N-box vs. E-box occupancy and integrate with target-gene expression.
Experiment: Structure-function dissection separating the WRPW/Groucho and PLSLV/CtBP interaction surfaces (point mutants) with transcriptional readouts at segmentation and proneural targets to define corepressor-specific target sets.
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