RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3.
Polycomb-repressive complex 1 (PRC1) has a central role in the regulation of heritable gene silencing during differentiation and development. PRC1 recruitment is generally attributed to interaction of the chromodomain of the core protein Polycomb with trimethyl histone H3K27 (H3K27me3), catalyzed by a second complex, PRC2. Unexpectedly we find that RING1B, the catalytic subunit of PRC1, and associated monoubiquitylation of histone H2A are targeted to closely overlapping sites in wild-type and PRC2-deficient mouse embryonic stem cells (mESCs), demonstrating an H3K27me3-independent pathway for recruitment of PRC1 activity. We show that this pathway is mediated by RYBP-PRC1, a complex comprising catalytic subunits of PRC1 and the protein RYBP. RYBP-PRC1 is recruited to target loci in mESCs and is also involved in Xist RNA-mediated silencing, the latter suggesting a wider role in Polycomb silencing. We discuss the implications of these findings for understanding recruitment and function of Polycomb repressors.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Lígia
L
Tavares
Emilia
E
Dimitrova
David
D
Oxley
Judith
J
Webster
Raymond
R
Poot
Jeroen
J
Demmers
Karel
K
Bezstarosti
Stephen
S
Taylor
Hiroki
H
Ura
Hiroshi
H
Koide
Anton
A
Wutz
Miguel
M
Vidal
Sarah
S
Elderkin
Neil
N
Brockdorff
D000818:Animals; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D051379:Mice; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
C107275:Eed protein, mouse; D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C120616:Rybp protein, mouse; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases