Simon Jeremy M, Parker Joel S, Liu Feng, Rothbart Scott B, Ait-Si-Ali Slimane, Strahl Brian D, Jin Jian, Davis Ian J, Mosley Amber L, Pattenden Samantha G
From the Carolina Institute for Developmental Disabilities, Department of Cell Biology and Physiology, and the Department of Genetics, Curriculum in Bioinformatics and Computational Biology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
the Department of Genetics and the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.
J Biol Chem. 2015 Oct 23;290(43):26088-102. doi: 10.1074/jbc.M115.654459. Epub 2015 Sep 3.
G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the majority of histone H3 lysine 9 mono- and di-methylation (H3K9me1/me2). Widely interspaced zinc finger (WIZ) associates with the G9a-GLP protein complex, but its role in mediating lysine methylation is poorly defined. Here, we show that WIZ regulates global H3K9me2 levels by facilitating the interaction of G9a with chromatin. Disrupting the association of G9a-GLP with chromatin by depleting WIZ resulted in altered gene expression and protein-protein interactions that were distinguishable from that of small molecule-based inhibition of G9a/GLP, supporting discrete functions of the G9a-GLP-WIZ chromatin complex in addition to H3K9me2 methylation.
G9a和GLP赖氨酸甲基转移酶形成一种异二聚体复合物,该复合物负责大部分组蛋白H3赖氨酸9单甲基化和二甲基化(H3K9me1/me2)。广泛间隔锌指蛋白(WIZ)与G9a-GLP蛋白复合物相关联,但其在介导赖氨酸甲基化中的作用尚不清楚。在此,我们表明WIZ通过促进G9a与染色质的相互作用来调节整体H3K9me2水平。通过耗尽WIZ破坏G9a-GLP与染色质的关联会导致基因表达和蛋白质-蛋白质相互作用发生改变,这与基于小分子抑制G9a/GLP的情况不同,这支持了除H3K9me2甲基化外,G9a-GLP-WIZ染色质复合物具有离散功能。