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

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 (Sp...

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Autores principales: 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, Yanhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822050/
https://www.ncbi.nlm.nih.gov/pubmed/27045799
http://dx.doi.org/10.1038/ncomms11197
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author 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, Yanhui
author_facet 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, Yanhui
author_sort Fang, Jian
collection PubMed
description 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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spelling pubmed-48220502016-04-17 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, Yanhui Nat Commun Article 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. Nature Publishing Group 2016-04-05 /pmc/articles/PMC4822050/ /pubmed/27045799 http://dx.doi.org/10.1038/ncomms11197 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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, Yanhui
Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
title Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
title_full Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
title_fullStr Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
title_full_unstemmed Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
title_short Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition
title_sort hemi-methylated dna opens a closed conformation of uhrf1 to facilitate its histone recognition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822050/
https://www.ncbi.nlm.nih.gov/pubmed/27045799
http://dx.doi.org/10.1038/ncomms11197
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