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Control of embryonic stem cell identity by BRD4-dependent transcriptional elongation of super-enhancer-associated pluripotency genes.
- Source :
-
Cell reports [Cell Rep] 2014 Oct 09; Vol. 9 (1), pp. 234-247. Date of Electronic Publication: 2014 Sep 26. - Publication Year :
- 2014
-
Abstract
- Transcription factors and chromatin-remodeling complexes are key determinants of embryonic stem cell (ESC) identity. Here, we demonstrate that BRD4, a member of the bromodomain and extraterminal domain (BET) family of epigenetic readers, regulates the self-renewal ability and pluripotency of ESCs. BRD4 inhibition resulted in induction of epithelial-to-mesenchymal transition (EMT) markers and commitment to the neuroectodermal lineage while reducing the ESC multidifferentiation capacity in teratoma assays. BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation. Our study describes a mechanism of regulation of ESC identity that could be applied to improve the efficiency of ESC differentiation.<br /> (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Cycle Proteins
Embryonic Stem Cells cytology
Embryonic Stem Cells metabolism
Gene Expression Regulation, Developmental
Humans
Mice
Pluripotent Stem Cells cytology
Pluripotent Stem Cells metabolism
Positive Transcriptional Elongation Factor B genetics
Positive Transcriptional Elongation Factor B metabolism
Transcription, Genetic
Embryonic Stem Cells physiology
Nuclear Proteins genetics
Nuclear Proteins metabolism
Pluripotent Stem Cells physiology
Transcription Factors genetics
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 25263550
- Full Text :
- https://doi.org/10.1016/j.celrep.2014.08.055