Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals
Qian Zhao, Jiqin Zhang, Ruoyu Chen, Lina Wang, Bo Li, Hao Cheng, Xiaoya Duan, Haijun Zhu, Wei Wei, Jiwen Li, Qihan Wu, Jing-Dong J. Han, Wenqiang Yu, Shaorong Gao, Guohong Li & Jiemin Wong 

Abstract

        In mammals it is unclear if UHRF1-mediated DNA maintenance methylation by DNMT1 is strictly dependent on histone H3K9 methylation. Here we have generated an Uhrf1 knockin (KI) mouse model that specifically abolishes the H3K9me2/3-binding activity of Uhrf1. The homozygous Uhrf1 KI mice are viable and fertile, and exhibit ∼10% reduction of DNA methylation in various tissues. The reduced DNA methylation occurs globally in the genome and does not restrict only to the H3K9me2/3 enriched repetitive sequences. In vitro UHRF1 binds with higher affinity to reconstituted nucleosome with hemi-methylated CpGs than that with H3K9me2/3, although it binds cooperatively to nucleosome with both modifications. We also show that the nucleosome positioning affects the binding of methylated DNA by UHRF1. Thus, while our study supports a role for H3K9 methylation in promoting DNA methylation, it demonstrates for the first time that DNA maintenance methylation in mammals is largely independent of H3K9 methylation.

See more about this article: http://www.nature.com/articles/ncomms12464