title: Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2.
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.
authors: 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.
authors: Xiaozhe
authors: X
authors: Xiong
authors: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
authors: Tatyana
authors: T
authors: Panchenko
authors: 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.
authors: Shuang
authors: S
authors: Yang
authors: 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.
authors: Shuai
authors: S
authors: Zhao
authors: 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.|School of Life Sciences, Tsinghua University, Beijing, China.
authors: Peiqiang
authors: P
authors: Yan
authors: School of Life Sciences, Tsinghua University, Beijing, China.|Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
authors: Wenhao
authors: W
authors: Zhang
authors: School of Life Sciences, Tsinghua University, Beijing, China.|Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
authors: Wei
authors: W
authors: Xie
authors: 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.|Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
authors: Yuanyuan
authors: Y
authors: Li
authors: Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois, USA.
authors: Yingming
authors: Y
authors: Zhao
authors: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, New York, USA.
authors: C David
authors: CD
authors: Allis
authors: 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.|Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.|Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors: Haitao
authors: http://orcid.org/0000-0002-6686-1677
authors: H
authors: Li
mesh_terms: D000107:Acetylation; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C113581:DPF2 protein, human; D006657:Histones; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human