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Mol Cell. 2016 Apr 21;62(2):181-193. doi: 10.1016/j.molcel.2016.03.028.

Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain.

Author information

1
MOE Key Laboratory of Protein Sciences, Department of Basic Medical Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Beijing 100084, PRC; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, PRC.
2
Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA.
3
Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
4
Ben May Department of Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
5
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
6
Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA. Electronic address: alliscd@mail.rockefeller.edu.
7
MOE Key Laboratory of Protein Sciences, Department of Basic Medical Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Beijing 100084, PRC; Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, PRC; Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PRC. Electronic address: lht@tsinghua.edu.cn.

Abstract

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.

PMID:
27105114
PMCID:
PMC4841940
DOI:
10.1016/j.molcel.2016.03.028
[Indexed for MEDLINE]
Free PMC Article

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