Distinct roles of GCN5/PCAF‐mediated H3K9ac and CBP/p300‐mediated H3K18/27ac in nuclear receptor transactivation
Open accessAbstract
Histone acetyltransferases (HATs) GCN5 and PCAF (GCN5/PCAF) and CBP and p300 (CBP/p300) are transcription co-activators. However, how these two distinct families of HATs regulate gene activation remains unclear. Here, we show deletion of GCN5/PCAF in cells specifically and dramatically reduces acetylation on histone H3K9 (H3K9ac) while deletion of CBP/p300 specifically and dramatically reduces acetylations on H3K18 and H3K27 (H3K18/27ac). A ligand for nuclear receptor (NR) PPARδ induces sequential enrichment of H3K18/27ac, RNA polymerase II (Pol II) and H3K9ac on PPARδ target gene Angptl4 promoter, which correlates with a robust Angptl4 expression. Inhibiting transcription elongation blocks ligand-induced H3K9ac, but not H3K18/27ac, on the Angptl4 promoter. Finally, we show GCN5/PCAF and GCN5/PCAF-mediated H3K9ac correlate with, but are surprisingly dispensable for, NR target gene activation. In contrast, CBP/p300 and their HAT activities are essential for ligand-induced Pol II recruitment on, and activation of, NR target genes. These results highlight the substrate and site specificities of HATs in cells, demonstrate the distinct roles of GCN5/PCAF- and CBP/p300-mediated histone acetylations in gene activation, and suggest an important role of CBP/p300-mediated H3K18/27ac in NR-dependent transcription.
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SWI/SNF recruits the chromatin activators P300 and CBP, which mediate acetylation of histone H3 lysine 27 through their intrinsic histone acetyltransferase activity.
“SWI/SNF recruits the chromatin activators P300 and CBP, which mediate the acetylation of histone H3 lysine 27 through their intrinsic histone acetyltransferase (HAT) activity [59–62].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [60]
The Introduction identifies CBP and p300 as histone acetyltransferase co-activators, and “Substrate and site specificities of CBP/p300” reports that they are required for over 90% of H3K27 acetylation in mouse embryonic fibroblasts. The cited paper does not establish the sentence’s additional claim that SWI/SNF recruits CBP and p300. (LLM, conf=0.88)
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- Authors
- Jin, Q., Yu, L., Wang, L., Zhang, Z., Kasper, L. H., Lee, J., Wang, C., Brindle, P. K., Dent, S. Y. R., & Ge, K.
- Affiliations
- National Institutes of Health (US)
- National Center for Toxicological Research (US)
- The University of Texas MD Anderson Cancer Center (US)
- St. Jude Children's Research Hospital (US)
- Corresponding author
- Ge, Kai
- ORCID
- Venue
- The EMBO Journal
- Published
- 2010-12-03
- Volume
- 30
- Issue
- 2
- Pages
- 249-262
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3025463
- OpenAlex
- W2158074192
- Cited by
- 877
- References
- 6
- Citations by year
- 2026: 40 · 2025: 54 · 2024: 79 · 2023: 70 · 2022: 50 · 2021: 66 · 2020: 82 · 2019: 59 · 2018: 62 · 2017: 54 · 2016: 50 · 2015: 51 · 2014: 63 · 2013: 50 · 2012: 33
- FWCI
- 12.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (Z99 DK999999)
- National Institute of General Medical Sciences (R01GM067718)
- National Institute of Diabetes and Digestive and Kidney Diseases (Z01DK075003, ZIADK047055, ZIADK075017, ZIADK075003)
- National Institute of Dental and Craniofacial Research (DE018183, R21DE018183)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- histone acetyltransferase, CBP/p300, H3K9 acetylation, nuclear receptor transactivation, PPARδ, ANGPTL4, RNA polymerase II recruitment, transcription elongation, gene activation
- MeSH terms
- Angiopoietin-Like Protein 4, p300-CBP-Associated Factor, Acetylation, Animals, Histones, Humans, Promoter Regions, Genetic, Mass Spectrometry, Substrate Specificity, Thiazoles, Blotting, Western, Transcriptional Activation, Reverse Transcriptase Polymerase Chain Reaction, Angiopoietins, Chromatin Immunoprecipitation, PPAR delta, p300-CBP Transcription Factors, E1A-Associated p300 Protein, Mice, Gene Knockout Techniques
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