Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition

Jian Fang; Jingdong Cheng; Jiaolong Wang; Qiao Zhang; Mengjie Liu; Rui Gong; Ping Wang; Xiaodan Zhang; Yangyang Feng; Wenxian Lan; Zhou Gong; Chun Tang; Jiemin Wong; Huirong Yang; Chunyang Cao; Yanhui Xu

doi:10.1038/ncomms11197

Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition

Jian Fang
, Jingdong Cheng
, Jiaolong Wang
, Qiao Zhang
, Mengjie Liu
, Rui Gong
, Ping Wang
, Xiaodan Zhang
, Yangyang Feng
, Wenxian Lan
, Zhou Gong
, Chun Tang
, Jiemin Wong
, Huirong Yang
, Chunyang Cao
, Yanhui Xu^*

^*Corresponding author for this work

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

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.

Original language	English
Article number	11197
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11197
State	Published - 5 Apr 2016

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@article{129d0b66a6174249966d303faf742589,

title = "Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition",

abstract = "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.",

author = "Jian Fang and Jingdong Cheng and Jiaolong Wang and Qiao Zhang and Mengjie Liu and Rui Gong and Ping Wang and Xiaodan Zhang and Yangyang Feng and Wenxian Lan and Zhou Gong and Chun Tang and Jiemin Wong and Huirong Yang and Chunyang Cao and Yanhui Xu",

year = "2016",

month = apr,

day = "5",

doi = "10.1038/ncomms11197",

language = "英语",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

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}

TY - JOUR

T1 - Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition

AU - Fang, Jian

AU - Cheng, Jingdong

AU - Wang, Jiaolong

AU - Zhang, Qiao

AU - Liu, Mengjie

AU - Gong, Rui

AU - Wang, Ping

AU - Zhang, Xiaodan

AU - Feng, Yangyang

AU - Lan, Wenxian

AU - Gong, Zhou

AU - Tang, Chun

AU - Wong, Jiemin

AU - Yang, Huirong

AU - Cao, Chunyang

AU - Xu, Yanhui

PY - 2016/4/5

Y1 - 2016/4/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84962636426

U2 - 10.1038/ncomms11197

DO - 10.1038/ncomms11197

M3 - 文章

C2 - 27045799

AN - SCOPUS:84962636426

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11197

ER -

Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition

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