Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
Fang Jian
Cheng Jingdong
Wang Jiaolong
Zhang Qiao
Liu Mengjie
Gong Rui
Wang Ping
Zhang Xiaodan
Feng Yangyang
Lan Wenxian
Gong Zhou
Tang Chun
Wong Jiemin
Yang Huirong
Cao Chunyang
Xu Yan-Hui
· 2016
期刊名称：
Nature Communications
2016 年
7 卷
摘要：
UHRF1 is an important epigenetic regulator for maintenance DNA methylation. UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown. Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition. Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD-PHD. The Spacer also facilitates UHRF1-DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA. When TTD-PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin. Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.
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