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Brookes, E.* ; de Santiago, I.* ; Hebenstreit, D.* ; Morris, K.J.* ; Carroll, T.* ; Xie, S.Q.* ; Stock, J.K.* ; Heidemann, M. ; Eick, D. ; Nozaki, N.* ; Kimura, H.* ; Ragoussis, J.* ; Teichmann, S.A.* ; Pombo, A.*

Polycomb associates genome-wide with a specific RNA polymerase II variant, and regulates metabolic genes in ESCs.

Cell Stem Cell 10, 157-170 (2012)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Embroyonic stem-cells; Transcription factors; Epigenetic states; Bivalent genes; Self-renewal; Differentiation; Pluripotency; Marks; SEQ; Heterogeneity
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Zeitschrift Cell Stem Cell
Quellenangaben Band: 10, Heft: 2, Seiten: 157-170 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed