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 () and Yanhui Xu ()
Additional contact information
Jian Fang: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Jingdong Cheng: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Jiaolong Wang: State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Qiao Zhang: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University
Mengjie Liu: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Rui Gong: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Ping Wang: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Xiaodan Zhang: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Yangyang Feng: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Wenxian Lan: State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Zhou Gong: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences
Chun Tang: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences
Jiemin Wong: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University
Huirong Yang: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University
Chunyang Cao: State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
Yanhui Xu: Key Laboratory of Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Shanghai Medical College of Fudan University

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms11197 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11197

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms11197

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().