enok (enoki mushroom) encodes the Drosophila KAT6 (MOZ/MORF) family MYST histone acetyltransferase. It is the catalytic subunit of the Enok complex, which also contains the bromodomain-PHD scaffold Br140 (BRPF homolog), the ING-family protein Ing5 and Eaf6. Enok is the main enzyme that acetylates histone H3 at lysine 23 (H3K23ac) in flies, and all complex subunits are needed for full activity. The complex binds the Elg1 PCNA-unloader complex and restrains PCNA unloading from chromatin to promote the G1/S transition. Enok acetylation activates transcription of specific genes; in the ovary it promotes expression of rhino and recruitment of Rhino to piRNA clusters, supporting piRNA production and transposon silencing. enok mutants arrest mushroom body neuroblast proliferation, and Enok is required in the germline and in niche cells to maintain female germline stem cells.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for chromatin (PTN004172926; donors include FB:FBgn0034975 enok itself, MGI:1919307, MGI:2182799, PomBase and SGD MYST proteins). Reason: Enok acetylates chromatin-bound H3 and affects chromatin-bound PCNA; chromatin is an appropriate location for the catalytic subunit. |
| GO:0000786 nucleosome | IEA GO_REF:0000120 | REMOVE | Summary: UniRule/InterPro (IPR005818, linker histone H1/H5 globular domain) mapping to nucleosome. Reason: The H15-like winged-helix domain in the KAT6 N-terminal region does not make Enok a structural nucleosome component; the mapping is appropriate only for linker histones. Supporting Evidence: file:DROME/enok/enok-deep-research-falcon.md Enok should therefore **not** be annotated as a linker histone. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: DNA binding inferred from the N-terminal H15-like winged-helix domain. Reason: KAT6 winged-helix domains are plausible DNA-binding modules, but there is no Drosophila evidence and DNA binding is not part of Enok's established function. |
| GO:0003682 chromatin binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA for chromatin binding (PTN004172926; donor MGI:2442415 Kat6b). Reason: Plausible for a chromatin-acting HAT; no fly-specific evidence, and the more informative activity is H3K23 acetylation. |
| GO:0003712 transcription coregulator activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA for transcription coregulator activity (PTN004172926; donors FB:FBgn0028387, SGD:S000005770, UniProtKB:Q8WYB5 KAT6B, Q92794 KAT6A). Reason: Correct but general; Enok activates transcription through H3K23 acetylation (e.g. rhino and piRNA clusters). Replace with GO:0003713 transcription coactivator activity. Proposed replacements: transcription coactivator activity Supporting Evidence: PMID:33524038 the Drosophila acetyltransferase Enok, which can activate transcription by acetylating H3K23 |
| GO:0003824 catalytic activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA prediction of catalytic activity. Reason: Correct but uninformative; replace with GO:0043994 histone H3K23 acetyltransferase activity, already annotated by IDA. Proposed replacements: histone H3K23 acetyltransferase activity |
| GO:0004402 histone acetyltransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: Electronic histone acetyltransferase activity from the MYST HAT domain. Reason: Correct but general; Enok is the major H3K23 acetyltransferase. Replace with GO:0043994, already annotated by IDA. Proposed replacements: histone H3K23 acetyltransferase activity Supporting Evidence: PMID:27198229 We previously reported that Enok functions as the major HAT for establishing the H3K23ac mark in flies |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Enok is nuclear. Reason: Correct; consistent with Enok acting on chromatin. Supporting Evidence: file:DROME/enok/enok-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Enok is nuclear. Reason: Correct; consistent with Enok acting on chromatin. Supporting Evidence: file:DROME/enok/enok-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to chromosome. Reason: Correct; Enok acts on chromatin, and this mapping is as precise as the source allows. Supporting Evidence: file:DROME/enok/enok-uniprot.txt Chromosome |
| GO:0006271 DNA strand elongation involved in DNA replication | IDA PMID:27198229 The Enok acetyltransferase complex interacts with Elg1 and n... | MODIFY | Summary: The Enok complex promotes the G1/S transition by restraining Elg1-mediated PCNA unloading. Reason: The study shows a G1/S block and reduced chromatin-bound PCNA after Enok depletion and an Enok complex-Elg1 interaction; it does not measure DNA strand elongation. Replace with GO:0000082 G1/S transition of mitotic cell cycle. Shared complex process treated identically across the four Enok complex subunits. Proposed replacements: G1/S transition of mitotic cell cycle Supporting Evidence: PMID:27198229 Depletion of Enok resulted in an Elg1-dependent block at the G1/S transition and reduced chromatin-bound PCNA levels. |
| GO:0006334 nucleosome assembly | IEA GO_REF:0000120 | REMOVE | Summary: UniRule/InterPro (IPR005818, linker histone H15 domain) mapping to nucleosome assembly. Reason: Derived from a linker-histone domain signature; no evidence that Enok assembles nucleosomes, and its known activity is histone acetylation. Supporting Evidence: file:DROME/enok/enok-deep-research-falcon.md Enok should therefore **not** be annotated as a linker histone. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based regulation of transcription. Reason: Correct but general; Enok activates transcription. Replace with GO:0045944 positive regulation of transcription by RNA polymerase II, already annotated by IMP. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | MODIFY | Summary: IBA for regulation of transcription by Pol II (PTN004172926). Reason: Correct but general; replace with GO:0045944 positive regulation of transcription by RNA polymerase II, already annotated by IMP. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0007405 neuroblast proliferation | IMP PMID:11231125 enok encodes a Drosophila putative histone acetyltransferase... | KEEP AS NON CORE | Summary: enok mutant mushroom body neuroblasts arrest proliferation. Reason: Clear mutant phenotype, but a developmental consequence of Enok's chromatin function in specific tissues rather than its core molecular role. Supporting Evidence: PMID:11231125 the mushroom body defect is due to an arrest in neuroblast proliferation rather than a failure of either cell fate switching or axon branching |
| GO:0010484 histone H3 acetyltransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA for histone H3 acetyltransferase activity (PTN000834868; donors FB:FBgn0034975 enok itself, MGI:2442415, UniProtKB:Q8WYB5, Q92794). Reason: Correct but less specific than the Drosophila evidence; replace with GO:0043994 histone H3K23 acetyltransferase activity, already annotated by IDA. Proposed replacements: histone H3K23 acetyltransferase activity |
| GO:0016319 mushroom body development | IMP PMID:11231125 enok encodes a Drosophila putative histone acetyltransferase... | KEEP AS NON CORE | Summary: enok mutants have mushroom bodies with reduced axonal structures. Reason: Developmental phenotype secondary to the neuroblast proliferation defect. Supporting Evidence: PMID:11231125 which when it is mutated gives rise to mushroom bodies with reduced axonal structures |
| GO:0036099 female germ-line stem cell population maintenance | IMP PMID:24120347 The Drosophila putative histone acetyltransferase Enok maint... | KEEP AS NON CORE | Summary: Enok is required in the germline and niche to maintain female germline stem cells. Reason: Tissue-specific developmental role downstream of Enok's acetyltransferase function. Supporting Evidence: PMID:24120347 Removal or knockdown of Enok in the germline causes a GSC maintenance defect. |
| GO:0040029 epigenetic regulation of gene expression | IEA GO_REF:0000117 | MODIFY | Summary: ARBA prediction of epigenetic regulation of gene expression. Reason: Correct but general; Enok's H3K23 acetylation activates transcription. Replace with GO:0045944 positive regulation of transcription by RNA polymerase II, already annotated by IMP. Proposed replacements: positive regulation of transcription by RNA polymerase II |
| GO:0043994 histone H3K23 acetyltransferase activity | IDA PMID:27198229 The Enok acetyltransferase complex interacts with Elg1 and n... | ACCEPT | Summary: Enok complex acetylates histone H3 at K23. Reason: Core catalytic activity; depletion of Enok or any complex subunit reduces H3K23ac. Supporting Evidence: PMID:27198229 We previously reported that Enok functions as the major HAT for establishing the H3K23ac mark in flies PMID:27198229 Depletion of any of the four subunits led to reductions in the H3K23ac levels without affecting the H3K14ac levels |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:33524038 Acetyltransferase Enok regulates transposon silencing and pi... | ACCEPT | Summary: Enok promotes rhino transcription by acetylating H3K23. Reason: Direct mutant evidence that Enok's acetylation activates transcription of specific genes. Supporting Evidence: PMID:33524038 Enok not only promotes rhino expression by acetylating H3K23 |
| GO:0061733 protein-lysine-acetyltransferase activity | IEA GO_REF:0000003 | MODIFY | Summary: EC-mapping-based protein-lysine acetyltransferase activity. Reason: Correct but general; replace with GO:0043994 histone H3K23 acetyltransferase activity, already annotated. Proposed replacements: histone H3K23 acetyltransferase activity |
| GO:0070775 H3 histone acetyltransferase complex | IEA GO_REF:0000117 | MODIFY | Summary: ARBA prediction of H3 histone acetyltransferase complex. Reason: Correct but general; replace with GO:0070776 MOZ/MORF histone acetyltransferase complex, its descendant, already annotated. Proposed replacements: MOZ/MORF histone acetyltransferase complex |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for MOZ/MORF complex (PTN000065047; donors FB:FBgn0034975 enok itself, UniProtKB:Q8WYB5 KAT6B, Q92794 KAT6A). Reason: Consistent with direct biochemical evidence in flies. |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IDA PMID:27198229 The Enok acetyltransferase complex interacts with Elg1 and n... | ACCEPT | Summary: Subunit of the Enok (KAT6, MOZ/MORF-type) acetyltransferase complex. Reason: Core complex. Enok, Br140, Ing5 and Eaf6 co-purify reciprocally and each is required for the complex's H3K23 acetylation; shared complex term treated identically across the four subunits. Supporting Evidence: PMID:27198229 MudPIT analysis of Flag affinity purifications of Flag-HA-tagged Enok, Br140, Eaf6, and Ing5 showed copurification of these four components. |
| GO:0070776 MOZ/MORF histone acetyltransferase complex | IPI PMID:27198229 The Enok acetyltransferase complex interacts with Elg1 and n... | ACCEPT | Summary: Enok co-purifies with Br140, Ing5 and Eaf6. Reason: Core complex; shared complex term. Supporting Evidence: PMID:27198229 MudPIT analysis of Flag affinity purifications of Flag-HA-tagged Enok, Br140, Eaf6, and Ing5 showed copurification of these four components. |
| GO:0140543 positive regulation of piRNA transcription | IMP PMID:33524038 Acetyltransferase Enok regulates transposon silencing and pi... | KEEP AS NON CORE | Summary: Enok enhances transcription of piRNA clusters by facilitating Rhino recruitment. Reason: Direct and specific, but a germline-restricted role downstream of Enok's general coactivator function. Supporting Evidence: PMID:33524038 is critical for piRNA production from 54% of piRNA clusters including 42AB |
| GO:2000737 negative regulation of stem cell differentiation | IGI PMID:24120347 The Drosophila putative histone acetyltransferase Enok maint... | KEEP AS NON CORE | Summary: Enok deficiency causes ectopic Bruno expression and GSC loss; genetic interaction with bam (FB:FBgn0000114). Reason: Germline stem cell role, peripheral to core acetyltransferase function. Supporting Evidence: PMID:24120347 Misexpression of Bruno in GSCs and their immediate descendants results in a GSC loss that can be exacerbated by incorporating one copy of enok mutant allele. |
| GO:2000737 negative regulation of stem cell differentiation | IMP PMID:24120347 The Drosophila putative histone acetyltransferase Enok maint... | KEEP AS NON CORE | Summary: Enok deficiency causes ectopic Bruno expression and GSC loss; genetic interaction with bam (FB:FBgn0000114). Reason: Germline stem cell role, peripheral to core acetyltransferase function. Supporting Evidence: PMID:24120347 Misexpression of Bruno in GSCs and their immediate descendants results in a GSC loss that can be exacerbated by incorporating one copy of enok mutant allele. |
Loading supporting content…
Download this section (compressed HTML)Q: Does the Enok complex's effect on PCNA unloading require its acetyltransferase activity, and if so what is acetylated (histones, PCNA or Elg1)?
Experiment: Rescue Enok-depleted S2 cells with wild-type or catalytically dead Enok and measure chromatin-bound PCNA and G1/S progression, to test whether acetyltransferase activity is needed to restrain Elg1-mediated PCNA unloading.
Loading supporting content…
Download this section (compressed HTML)enoki mushroom (enok) encodes a MYST family histone acetyltransferase that acetylates lysine residues on histones, including H3K23, to regulate gene transcription. It contributes to stem cell self-renewal, oogenesis and neural development.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)