Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing.
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.
Schoeftner
Stefan
S
Research Institute of Molecular Pathology, Vienna, Austria.
Sengupta
Aditya K
AK
Kubicek
Stefan
S
Mechtler
Karl
K
Spahn
Laura
L
Koseki
Haruhiko
H
Jenuwein
Thomas
T
Wutz
Anton
A
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
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