5XTZ

Crystal structure of GAS41 YEATS bound to H3K27ac peptide

5XTZ の概要

• エントリーDOI: 10.2210/pdb5xtz/pdb
• 分子名称: YEATS domain-containing protein 4, THR-LYS-ALA-ALA-ARG-ALY-SER-ALA-PRO-ALA, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: epigenetic, histone acetylation, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 76364.78

構造登録者

Li, H.T.,Zhao, D. (登録日: 2017-06-21, 公開日: 2018-06-27, 最終更新日: 2024-10-30)

主引用文献

Hsu, C.C.,Zhao, D.,Shi, J.,Peng, D.,Guan, H.,Li, Y.,Huang, Y.,Wen, H.,Li, W.,Li, H.,Shi, X.
Gas41 links histone acetylation to H2A.Z deposition and maintenance of embryonic stem cell identity.
Cell Discov, 4:28-28, 2018

PubMed Abstract: The histone variant H2A.Z is essential for maintaining embryonic stem cell (ESC) identity in part by keeping developmental genes in a poised bivalent state. However, how H2A.Z is deposited into the bivalent domains remains unknown. In mammals, two chromatin remodeling complexes, Tip60/p400 and SRCAP, exchange the canonical histone H2A for H2A.Z in the chromatin. Here we show that Glioma Amplified Sequence 41 (Gas41), a shared subunit of the two H2A.Z-depositing complexes, functions as a reader of histone lysine acetylation and recruits Tip60/p400 and SRCAP to deposit H2A.Z into specific chromatin regions including bivalent domains. The YEATS domain of Gas41 bound to acetylated histone H3K27 and H3K14 both in vitro and in cells. The crystal structure of the Gas41 YEATS domain in complex with the H3K27ac peptide revealed that, similar to the AF9 and ENL YEATS domains, Gas41 YEATS forms a serine-lined aromatic cage for acetyllysine recognition. Consistently, mutations in the aromatic residues of the Gas41 YEATS domain abrogated the interaction. In mouse ESCs, knockdown of Gas41 led to flattened morphology of ESC colonies, as the result of derepression of differentiation genes. Importantly, the abnormal morphology was rescued by expressing wild-type Gas41, but not the YEATS domain mutated counterpart that does not recognize histone acetylation. Mechanically, we found that Gas41 depletion led to reduction of H2A.Z levels and a concomitant reduction of H3K27me3 levels on bivalent domains. Together, our study reveals an essential role of the Gas41 YEATS domain in linking histone acetylation to H2A.Z deposition and maintenance of ESC identity.

PubMed: 29900004
DOI: 10.1038/s41421-018-0027-0

実験手法

X-RAY DIFFRACTION (2.105 Å)