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Nat Chem Biol. 2016 Dec;12(12):1111-1118. doi: 10.1038/nchembio.2218. Epub 2016 Oct 24.

Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.

Author information

1
MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
2
Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
3
School of Life Sciences, Tsinghua University, Beijing, China.
4
Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
5
Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
6
Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Recognition of histone covalent modifications by 'reader' modules constitutes a major mechanism for epigenetic regulation. A recent upsurge of newly discovered histone lysine acylations, such as crotonylation (Kcr), butyrylation (Kbu), and propionylation (Kpr), greatly expands the coding potential of histone lysine modifications. Here we demonstrate that the histone acetylation-binding double PHD finger (DPF) domains of human MOZ (also known as KAT6A) and DPF2 (also known as BAF45d) accommodate a wide range of histone lysine acylations with the strongest preference for Kcr. Crystal structures of the DPF domain of MOZ in complex with H3K14cr, H3K14bu, and H3K14pr peptides reveal that these non-acetyl acylations are anchored in a hydrophobic 'dead-end' pocket with selectivity for crotonylation arising from intimate encapsulation and an amide-sensing hydrogen bonding network. Immunofluorescence and chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) showed that MOZ and H3K14cr colocalize in a DPF-dependent manner. Our studies call attention to a new regulatory mechanism centered on histone crotonylation readout by DPF family members.

PMID:
27775714
PMCID:
PMC5253430
DOI:
10.1038/nchembio.2218
[Indexed for MEDLINE]
Free PMC Article

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