5B73

Crystal structure of human ZMYND8 PHD-Bromo-PWWP domain

5B73 の概要

• エントリーDOI: 10.2210/pdb5b73/pdb
• 分子名称: Protein kinase C-binding protein 1, ZINC ION (3 entities in total)
• 機能のキーワード: zinc finger protein, metal binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39260.30

構造登録者

Li, H.,Li, Y.,Zheng, X. (登録日: 2016-06-03, 公開日: 2016-11-02, 最終更新日: 2024-03-20)

主引用文献

Li, N.,Li, Y.,Lv, J.,Zheng, X.,Wen, H.,Shen, H.,Zhu, G.,Chen, T.Y.,Dhar, S.S.,Kan, P.Y.,Wang, Z.,Shiekhattar, R.,Shi, X.,Lan, F.,Chen, K.,Li, W.,Li, H.,Lee, M.G.
ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes
Mol.Cell, 63:470-484, 2016

PubMed Abstract: Histone acetylation, including acetylated H3K14 (H3K14ac), is generally linked to gene activation. Monomethylated histone H3 lysine 4 (H3K4me1), together with other gene-activating marks, denotes active genes. In contrast to usual gene-activating functions of H3K14ac and H3K4me1, we here show that the dual histone modification mark H3K4me1-H3K14ac is recognized by ZMYND8 (also called RACK7) and can function to counteract gene expression. We identified ZMYND8 as a transcriptional corepressor of the H3K4 demethylase JARID1D. ZMYND8 antagonized the expression of metastasis-linked genes, and its knockdown increased the cellular invasiveness in vitro and in vivo. The plant homeodomain (PHD) and Bromodomain cassette in ZMYND8 mediated the combinatorial recognition of H3K4me1-H3K14ac and H3K4me0-H3K14ac by ZMYND8. These findings uncover an unexpected role for the signature H3K4me1-H3K14ac in attenuating gene expression and reveal a metastasis-suppressive epigenetic mechanism in which ZMYND8's PHD-Bromo cassette couples H3K4me1-H3K14ac with downregulation of metastasis-linked genes.

PubMed: 27477906
DOI: 10.1016/j.molcel.2016.06.035

実験手法

X-RAY DIFFRACTION (1.8 Å)