Journal
STEM CELLS
Volume 37, Issue 8, Pages 1018-1029Publisher
WILEY
DOI: 10.1002/stem.3025
Keywords
Pluripotent stem cells; hnRNP-K; Oct4; Pou5f1; Chromatin; Histone code
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Funding
- Russian Science Foundation (RSF) [17-14-01407]
- Russian Foundation for Basic Research (RFBR) [17-00-00324]
- joint tri-lateral Volkswagen Germany-Russia-Ukraine grant
- [DFG-ON86/4-2]
- Russian Science Foundation [17-14-01407] Funding Source: Russian Science Foundation
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The transcription factor Oct4 plays a key regulatory role in the induction and maintenance of cellular pluripotency. In this article, we show that ubiquitous and multifunctional poly(C) DNA/RNA-binding protein hnRNP-K occupies Oct4 (Pou5f1) enhancers in embryonic stem cells (ESCs) but is dispensable for the initiation, maintenance, and downregulation of Oct4 gene expression. Nevertheless, hnRNP-K has an essential cell-autonomous function in ESCs to maintain their proliferation and viability. To better understand mechanisms of hnRNP-K action in ESCs, we have performed ChIP-seq analysis of genome-wide binding of hnRNP-K and identified several thousands of hnRNP-K target sites that are frequently co-occupied by pluripotency-related and common factors (Oct4, TATA-box binding protein, Sox2, Nanog, Otx2, etc.), as well as active histone marks. Furthermore, hnRNP-K localizes exclusively within open chromatin, implying its role in the onset and/or maintenance of this chromatin state.
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