PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation

Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long non-coding RNAs. Here we show that the non-canonical PCGF3/5-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5-PRC1...

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Main Authors: Almeida, M, Pintacuda, G, Masui, O, Koseki, Y, Gdula, M, Cerase, A, Brown, D, Mould, A, Innocent, C, Nakayama, M, Schermelleh, L, Nesterova, T, Koseki, H, Brockdorff, N
Format: Journal article
Language:English
Published: American Association for the Advancement of Science 2017
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author Almeida, M
Pintacuda, G
Masui, O
Koseki, Y
Gdula, M
Cerase, A
Brown, D
Mould, A
Innocent, C
Nakayama, M
Schermelleh, L
Nesterova, T
Koseki, H
Brockdorff, N
author_facet Almeida, M
Pintacuda, G
Masui, O
Koseki, Y
Gdula, M
Cerase, A
Brown, D
Mould, A
Innocent, C
Nakayama, M
Schermelleh, L
Nesterova, T
Koseki, H
Brockdorff, N
author_sort Almeida, M
collection OXFORD
description Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long non-coding RNAs. Here we show that the non-canonical PCGF3/5-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5-PRC1 mediated ubiquitylation of histone H2A signals recruitment of other non-canonical PRC1 complexes, and of PRC2, leading to deposition of histone H3 lysine 27 methylation chromosome wide. Pcgf3/5 gene knockout results in female specific embryo lethality, and abrogates Xist mediated gene repression, highlighting a key role for Polycomb in Xist dependent chromosome silencing. Our findings overturn existing models for Polycomb recruitment by Xist RNA, and moreover establish precedence for H2AK119u1 in initiating Polycomb domain formation in a physiological context.
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spelling oxford-uuid:132032ac-36e3-464f-9fe1-94ee7de7de872022-03-26T10:12:06ZPCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:132032ac-36e3-464f-9fe1-94ee7de7de87EnglishSymplectic Elements at OxfordAmerican Association for the Advancement of Science2017Almeida, MPintacuda, GMasui, OKoseki, YGdula, MCerase, ABrown, DMould, AInnocent, CNakayama, MSchermelleh, LNesterova, TKoseki, HBrockdorff, NRecruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long non-coding RNAs. Here we show that the non-canonical PCGF3/5-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5-PRC1 mediated ubiquitylation of histone H2A signals recruitment of other non-canonical PRC1 complexes, and of PRC2, leading to deposition of histone H3 lysine 27 methylation chromosome wide. Pcgf3/5 gene knockout results in female specific embryo lethality, and abrogates Xist mediated gene repression, highlighting a key role for Polycomb in Xist dependent chromosome silencing. Our findings overturn existing models for Polycomb recruitment by Xist RNA, and moreover establish precedence for H2AK119u1 in initiating Polycomb domain formation in a physiological context.
spellingShingle Almeida, M
Pintacuda, G
Masui, O
Koseki, Y
Gdula, M
Cerase, A
Brown, D
Mould, A
Innocent, C
Nakayama, M
Schermelleh, L
Nesterova, T
Koseki, H
Brockdorff, N
PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation
title PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation
title_full PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation
title_fullStr PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation
title_full_unstemmed PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation
title_short PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation
title_sort pcgf3 5 prc1 initiates polycomb recruitment in x chromosome inactivation
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