Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation

Abstract Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the mainten...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08433a10a663408cb2881ea8919a7717
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:08433a10a663408cb2881ea8919a7717
record_format	dspace
spelling	oai:doaj.org-article:08433a10a663408cb2881ea8919a77172021-12-02T12:30:54ZUsp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation10.1038/s41598-017-00136-52045-2322https://doaj.org/article/08433a10a663408cb2881ea8919a77172017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00136-5https://doaj.org/toc/2045-2322Abstract Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA methylation.Luna YamaguchiAtsuya NishiyamaToshinori MisakiYoshikazu JohmuraJun UedaKyohei AritaKoji NagaoChikashi ObuseMakoto NakanishiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luna Yamaguchi Atsuya Nishiyama Toshinori Misaki Yoshikazu Johmura Jun Ueda Kyohei Arita Koji Nagao Chikashi Obuse Makoto Nakanishi Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
description	Abstract Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA methylation.
format	article
author	Luna Yamaguchi Atsuya Nishiyama Toshinori Misaki Yoshikazu Johmura Jun Ueda Kyohei Arita Koji Nagao Chikashi Obuse Makoto Nakanishi
author_facet	Luna Yamaguchi Atsuya Nishiyama Toshinori Misaki Yoshikazu Johmura Jun Ueda Kyohei Arita Koji Nagao Chikashi Obuse Makoto Nakanishi
author_sort	Luna Yamaguchi
title	Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
title_short	Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
title_full	Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
title_fullStr	Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
title_full_unstemmed	Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
title_sort	usp7-dependent histone h3 deubiquitylation regulates maintenance of dna methylation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/08433a10a663408cb2881ea8919a7717
work_keys_str_mv	AT lunayamaguchi usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT atsuyanishiyama usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT toshinorimisaki usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT yoshikazujohmura usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT junueda usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT kyoheiarita usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT kojinagao usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT chikashiobuse usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation AT makotonakanishi usp7dependenthistoneh3deubiquitylationregulatesmaintenanceofdnamethylation
_version_	1718394257388077056

Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation

Ejemplares similares