title: Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing.
abstract: In mammals X inactivation is initiated by expression of Xist RNA and involves the recruitment of Polycomb repressive complex 1 (PRC1) and 2 (PRC2), which mediate chromosome-wide ubiquitination of histone H2A and methylation of histone H3, respectively. Here, we show that PRC1 recruitment by Xist RNA is independent of gene silencing. We find that Eed is required for the recruitment of the canonical PRC1 proteins Mph1 and Mph2 by Xist. However, functional Ring1b is recruited by Xist and mediates ubiquitination of histone H2A in Eed deficient embryonic stem (ES) cells, which lack histone H3 lysine 27 tri-methylation. Xist expression early in ES cell differentiation establishes a chromosomal memory, which allows efficient H2A ubiquitination in differentiated cells and is independent of silencing and PRC2. Our data show that Xist recruits PRC1 components by both PRC2 dependent and independent modes and in the absence of PRC2 function is sufficient for the establishment of Polycomb-based memory systems in X inactivation.
authors.affiliation: Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schoeftner
authors.forename: Aditya K
authors.initials: AK
authors.lastname: Sengupta
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicek
authors.forename: Karl
authors.initials: K
authors.lastname: Mechtler
authors.forename: Laura
authors.initials: L
authors.lastname: Spahn
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Anton
authors.initials: A
authors.lastname: Wutz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004622:Embryo, Mammalian / Q000166:cytology; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D020868:Gene Silencing; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000502:physiology; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D049951:X Chromosome Inactivation
chemical_list: D004268:DNA-Binding Proteins; C107275:Eed protein, mouse; D006657:Histones; D063146:Polycomb-Group Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; C494163:Suz12 protein, mouse; C077885:XIST non-coding RNA; D012313:RNA; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases