A Functional Link between Nuclear RNA Decay and Transcriptional Control Mediated by the Polycomb Repressive Complex 2
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A Functional Link between Nuclear RNA Decay and Transcriptional Control Mediated by the Polycomb Repressive Complex 2. / Garland, William; Comet, Itys; Wu, Mengjun; Radzisheuskaya, Aliaksandra; Rib, Leonor; Vitting-Seerup, Kristoffer; Lloret-Llinares, Marta; Sandelin, Albin; Helin, Kristian; Jensen, Torben Heick.
I: Cell Reports, Bind 29, Nr. 7, 2019, s. 1800-1811.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - A Functional Link between Nuclear RNA Decay and Transcriptional Control Mediated by the Polycomb Repressive Complex 2
AU - Garland, William
AU - Comet, Itys
AU - Wu, Mengjun
AU - Radzisheuskaya, Aliaksandra
AU - Rib, Leonor
AU - Vitting-Seerup, Kristoffer
AU - Lloret-Llinares, Marta
AU - Sandelin, Albin
AU - Helin, Kristian
AU - Jensen, Torben Heick
N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Pluripotent embryonic stem cells (ESCs) constitute an essential cellular niche sustained by epigenomic and transcriptional regulation. Any role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the poly(A) RNA exosome targeting (PAXT) connection, and transcriptional control by the polycomb repressive complex 2 (PRC2). Knockout of the PAXT component ZFC3H1 impairs mouse ESC differentiation. In addition to the upregulation of bona fide PAXT substrates, Zfc3h1-/- cells abnormally express developmental genes usually repressed by PRC2. Such de-repression is paralleled by decreased PRC2 binding to chromatin and low PRC2-directed H3K27 methylation. PRC2 complex stability is compromised in Zfc3h1-/- cells with elevated levels of unspecific RNA bound to PRC2 components. We propose that excess RNA hampers PRC2 function through its sequestration from DNA. Our results highlight the importance of balancing nuclear RNA levels and demonstrate the capacity of bulk RNA to regulate chromatin-associated proteins.
AB - Pluripotent embryonic stem cells (ESCs) constitute an essential cellular niche sustained by epigenomic and transcriptional regulation. Any role of post-transcriptional processes remains less explored. Here, we identify a link between nuclear RNA levels, regulated by the poly(A) RNA exosome targeting (PAXT) connection, and transcriptional control by the polycomb repressive complex 2 (PRC2). Knockout of the PAXT component ZFC3H1 impairs mouse ESC differentiation. In addition to the upregulation of bona fide PAXT substrates, Zfc3h1-/- cells abnormally express developmental genes usually repressed by PRC2. Such de-repression is paralleled by decreased PRC2 binding to chromatin and low PRC2-directed H3K27 methylation. PRC2 complex stability is compromised in Zfc3h1-/- cells with elevated levels of unspecific RNA bound to PRC2 components. We propose that excess RNA hampers PRC2 function through its sequestration from DNA. Our results highlight the importance of balancing nuclear RNA levels and demonstrate the capacity of bulk RNA to regulate chromatin-associated proteins.
U2 - 10.1016/j.celrep.2019.10.011
DO - 10.1016/j.celrep.2019.10.011
M3 - Journal article
C2 - 31722198
VL - 29
SP - 1800
EP - 1811
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 7
ER -
ID: 230434493