Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain
Open accessAbstract
Recognition of histone covalent modifications by chromatin-binding protein modules ("readers") constitutes a major mechanism for epigenetic regulation, typified by bromodomains that bind acetyllysine. Non-acetyl histone lysine acylations (e.g., crotonylation, butyrylation, propionylation) have been recently identified, but readers that prefer these acylations have not been characterized. Here we report that the AF9 YEATS domain displays selectively higher binding affinity for crotonyllysine over acetyllysine. Structural studies revealed an extended aromatic sandwiching cage with crotonyl specificity arising from π-aromatic and hydrophobic interactions between crotonyl and aromatic rings. These features are conserved among the YEATS, but not the bromodomains. Using a cell-based model, we showed that AF9 co-localizes with crotonylated histone H3 and positively regulates gene expression in a YEATS domain-dependent manner. Our studies define the evolutionarily conserved YEATS domain as a family of crotonyllysine readers and specifically demonstrate that the YEATS domain of AF9 directly links histone crotonylation to active transcription.
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Lysine acetylation and lysine crotonylation are recognized by distinct readers, in bromodomains and Yeats domains respectively.
“However, Lys-ac and Lys-cr may be interpreted differently, since they are recognized by distinct readers, in the bromodomain10 and Yeats domain11 respectively.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [11]
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References 32 · Cited by 384
- Authors
- Li, Y., Sabari, B. R., Panchenko, T., Wen, H., Zhao, D., Guan, H., Wan, L., Huang, H., Tang, Z., Zhao, Y., Roeder, R. G., Shi, X., Allis, C. D., & Li, H.
- Affiliations
- Center for Life Sciences (CN)
- Rockefeller University (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Chicago (US)
- Sichuan University (CN)
- Corresponding author
- Allis, C. David
- Li, Haitao
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 62
- Issue
- 2
- Pages
- 181-193
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC4841940
- OpenAlex
- W2339772771
- Cited by
- 384
- References
- 32
- Citations by year
- 2026: 41 · 2025: 40 · 2024: 49 · 2023: 37 · 2022: 41 · 2021: 43 · 2020: 30 · 2019: 28 · 2018: 28 · 2017: 34 · 2016: 13
- FWCI
- 17.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China (91519304)
- National Cancer Institute
- Major State Basic Research Development Program of China (2015CB910503)
- Welch Foundation (G1719)
- Cancer Prevention and Research Institute of Texas (RP160237)
- Leukemia and Lymphoma Society
- Rockefeller University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- histone crotonylation, AF9, YEATS domain, histone reader proteins, histone H3, transcriptional regulation, epigenetic regulation, bromodomain, protein structure, histone acylation
- MeSH terms
- RAW 264.7 Cells, Protein Domains, Bromodomain Containing Proteins, Acetylation, Animals, Binding Sites, Crotonates, Histones, Humans, Lysine, Models, Molecular, Mutation, Nuclear Proteins, Protein Processing, Post-Translational, Transcription Factors, Transcription, Genetic, Transfection, Transcriptional Activation, RNA-Binding Proteins, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Mice, HEK293 Cells, Hydrophobic and Hydrophilic Interactions
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