The bromodomain of Gcn5 regulates site specificity of lysine acetylation on histone H3.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:25106422", "kind": "science-record", "revision": 2, "content_hash": "sha256:2272594afecb1f9057ba77a242925d20803f9afee77a2932a1b86ecf0e64b118", "created_at": "2026-11-01T15:40:05Z", "updated_at": "2026-11-01T18:47:08Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The bromodomain of Gcn5 regulates site specificity of lysine acetylation on histone H3.", "doi": "10.1074/mcp.M114.038174", "pmid": "25106422", "authors": ["Anne M Cieniewicz", "Linley Moreland", "Alison E Ringel", "Samuel G Mackintosh", "Ana Raman", "Tonya M Gilbert", "Cynthia Wolberger", "Alan J Tackett", "Sean D Taverna"], "journal": "Molecular & cellular proteomics : MCP", "year": 2014, "abstract": "In yeast, the conserved histone acetyltransferase (HAT) Gcn5 associates with Ada2 and Ada3 to form the catalytic module of the ADA and SAGA transcriptional coactivator complexes. Gcn5 also contains an acetyl-lysine binding bromodomain that has been implicated in regulating nucleosomal acetylation in vitro, as well as at gene promoters in cells. However, the contribution of the Gcn5 bromodomain in regulating site specificity of HAT activity remains unclear. Here, we used a combined acid-urea gel and quantitative mass spectrometry approach to compare the HAT activity of wild-type and Gcn5 bromodomain-mutant ADA subcomplexes (Gcn5-Ada2-Ada3). Wild-type ADA subcomplex acetylated H3 lysines with the following specificity; H3K14 > H3K23 > H3K9 ≈ H3K18 > H3K27 > H3K36. However, when the Gcn5 bromodomain was defective in acetyl-lysine binding, the ADA subcomplex demonstrated altered site-specific acetylation on free and nucleosomal H3, with H3K18ac being the most severely diminished. H3K18ac was also severely diminished on H3K14R, but not H3K23R, substrates in wild-type HAT reactions, further suggesting that Gcn5-catalyzed acetylation of H3K14 and bromodomain binding to H3K14ac are important steps preceding H3K18ac. In sum, this work details a previously uncharacterized cross-talk between the Gcn5 bromodomain \"reader\" function and enzymatic HAT activity that might ultimately affect gene expression. Future studies of how mutations in bromodomains or other histone post-translational modification readers can affect chromatin-templated enzymatic activities will yield unprecedented insight into a potential \"histone/epigenetic code.\" MS data are available via ProteomeXchange with identifier PXD001167.", "claims": [{"id": "claim-target-result", "statement": "No statistical method is specified; the paper used a combined acid-urea gel and quantitative mass spectrometry approach, and the MS source data are available through ProteomeXchange under identifier PXD001167.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:25106422", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Here, we used a combined acid-urea gel and quantitative mass spectrometry approach to compare the HAT activity of wild-type and Gcn5 bromodomain-mutant ADA subcomplexes (Gcn5-Ada2-Ada3)."}, {"asset": "source:pmid:25106422", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "MS data are available via ProteomeXchange with identifier PXD001167."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "No statistical method is specified; the paper used a combined acid-urea gel and quantitative mass spectrometry approach, and the MS source data are available through ProteomeXchange under identifier PXD001167.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:25106422"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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