染色质
生物
二价染色质
组蛋白甲基化
组蛋白
组蛋白甲基转移酶
细胞生物学
表观遗传学
组蛋白密码
组蛋白H3
遗传学
组蛋白H1
核小体
分子生物学
DNA甲基化
基因
基因表达
作者
Sean E. Healton,Hugo Borges Pinto,Laxmi Mishra,Gregory A. Hamilton,Justin C. Wheat,Kalina Swist-Rosowska,Nicholas Shukeir,Yali Dou,Ulrich Steidl,Thomas Jenuwein,Matthew J. Gamble,Arthur I. Skoultchi
标识
DOI:10.1073/pnas.1920725117
摘要
Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de-repression of several classes of repetitive sequences, including major satellite, LINE-1, and ERV. Activation of repetitive sequence transcription is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant repressive mechanism for silencing of repetitive major satellite sequences. Our findings elucidate two distinct, H1-mediated pathways for silencing heterochromatin.
科研通智能强力驱动
Strongly Powered by AbleSci AI