A central role for canonical PRC1 in shaping the 3D nuclear landscape.
embryonic stem cells
epigenetics
gene regulation
gene repression
histone modifications
nuclear organization
polycomb
topologically associating domains (TADs)
Journal
Genes & development
ISSN: 1549-5477
Titre abrégé: Genes Dev
Pays: United States
ID NLM: 8711660
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
08
01
2020
accepted:
13
04
2020
pubmed:
23
5
2020
medline:
11
11
2020
entrez:
23
5
2020
Statut:
ppublish
Résumé
Polycomb group (PcG) proteins silence gene expression by chemically and physically modifying chromatin. A subset of PcG target loci are compacted and cluster in the nucleus; a conformation that is thought to contribute to gene silencing. However, how these interactions influence gross nuclear organization and their relationship with transcription remains poorly understood. Here we examine the role of Polycomb-repressive complex 1 (PRC1) in shaping 3D genome organization in mouse embryonic stem cells (mESCs). Using a combination of imaging and Hi-C analyses, we show that PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at a megabase scale. Impairment of PRC1 enzymatic activity does not directly disrupt these interactions. We demonstrate that PcG targets coalesce in vivo, and that developmentally induced expression of one of the target loci disrupts this spatial arrangement. Finally, we show that transcriptional activation and the loss of PRC1-mediated interactions are separable events. These findings provide important insights into the function of PRC1, while highlighting the complexity of this regulatory system.
Identifiants
pubmed: 32439634
pii: gad.336487.120
doi: 10.1101/gad.336487.120
pmc: PMC7328521
doi:
Substances chimiques
CCCTC-Binding Factor
0
Ctcf protein, mouse
0
Polycomb-Group Proteins
0
Polycomb Repressive Complex 1
EC 2.3.2.27
Rnf2 protein, mouse
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
931-949Subventions
Organisme : Medical Research Council
ID : MC_UU_00007/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S007644/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K017047/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBSRC_BB/H008500/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 Boyle et al.; Published by Cold Spring Harbor Laboratory Press.
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