Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.
Polycomb repressor complexes (PRCs) are important chromatin modifiers fundamentally implicated in pluripotency and cancer. Polycomb silencing in embryonic stem cells (ESCs) can be accompanied by active chromatin and primed RNA polymerase II (RNAPII), but the relationship between PRCs and RNAPII remains unclear genome-wide. We mapped PRC repression markers and four RNAPII states in ESCs using ChIP-seq, and found that PRC targets exhibit a range of RNAPII variants. First, developmental PRC targets are bound by unproductive RNAPII (S5p(+)S7p(-)S2p(-)) genome-wide. Sequential ChIP, Ring1B depletion, and genome-wide correlations show that PRCs and RNAPII-S5p physically bind to the same chromatin and functionally synergize. Second, we identify a cohort of genes marked by PRC and elongating RNAPII (S5p(+)S7p(+)S2p(+)); they produce mRNA and protein, and their expression increases upon PRC1 knockdown. We show that this group of PRC targets switches between active and PRC-repressed states within the ESC population, and that many have roles in metabolism.
Genome Function Group, MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Emily
E
Brookes
Inês
I
de Santiago
Daniel
D
Hebenstreit
Kelly J
KJ
Morris
Tom
T
Carroll
Sheila Q
SQ
Xie
Julie K
JK
Stock
Martin
M
Heidemann
Dirk
D
Eick
Naohito
N
Nozaki
Hiroshi
H
Kimura
Jiannis
J
Ragoussis
Sarah A
SA
Teichmann
Ana
A
Pombo
D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D055106:Genome-Wide Association Study; D051379:Mice; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011485:Protein Binding / Q000235:genetics; D021381:Protein Transport; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II