Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity Journal Article

   

Authors:	Finley, L. W. S.; Vardhana, S. A.; Carey, B. W.; Alonso-Curbelo, D.; Koche, R.; Chen, Y.; Wen, D.; King, B.; Radler, M. R.; Rafii, S.; Lowe, S. W.; Allis, C. D.; Thompson, C. B.
Article Title:	Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity
Abstract:	A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. In metastable ESCs, Brd4 independence can be achieved by increased expression of pluripotency transcription factors, including STAT3, Nanog or Klf4, so long as the DNA methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is not essential for ESC self-renewal. Rather, the levels of pluripotency transcription factor abundance and Tet1/2 function determine the extent to which bromodomain recognition of protein acetylation contributes to the maintenance of gene expression and cell identity. © 2018 The Author(s).
Keywords:	protein expression; ten eleven translocation 1; ten eleven translocation 2; unclassified drug; human cell; nonhuman; binding affinity; protein function; protein analysis; animal cell; mouse; gene; stat3 protein; gene expression; embryo; embryonic stem cell; cell protein; molecular dynamics; rna; transcription regulation; chromatin; chromatin immunoprecipitation; histone h3; binding site; pluripotent stem cell; oxidoreductase; octamer transcription factor 4; transcription factor sox2; short hairpin rna; transcription factor nanog; kruppel like factor 4; intracellular signaling; dna methyltransferase 3a; pluripotency; histone acetylation; polycomb repressive complex 2; chromatin accessibility; cellular parameters; gene knockdown; human; male; priority journal; article; stem cell self-renewal; bromodomain containing protein 4; single guide rna
Journal Title:	Nature Cell Biology
Volume:	20
Issue:	5
ISSN:	1465-7392
Publisher:	Nature Publishing Group
Date Published:	2018-05-01
Start Page:	565
End Page:	574
Language:	English
DOI:	10.1038/s41556-018-0086-3
PROVIDER:	scopus
PMCID:	PMC5937285
PUBMED:	29662175
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045472698&doi=10.1038%2fs41556-018-0086-3&partnerID=40&md5=a199c0f1b525cc0a21e1ca9f5ebc3313
Notes:	Article -- Export Date: 1 June 2018 -- Source: Scopus

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