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

Journal article

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.

Authors: Almeida, M; Pintacuda, G; Masui, O; Koseki, Y; Gdula, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association for the Advancement of Science
• Journal: Science
• Volume: 356
• Issue: 6342
• Pages: 1081-1084
• Publication date: 2017-06-09
• Acceptance date: 2017-05-12
• DOI: 10.1126/science.aal2512
• EISSN: 1095-9203
• ISSN: 0036-8075
• Language: English
• Keywords: Letter