hnRNP-K targets open chromatin in mouse embryonic stem cells in concert with multiple regulators

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Item Type:	Article
Title:	hnRNP-K targets open chromatin in mouse embryonic stem cells in concert with multiple regulators
Creators Name:	Bakhmet, E.I., Nazarov, I.B., Gazizova, A.R., Vorobyeva, N.E., Kuzmin, A.A., Gordeev, M.N., Sinenko, S.A., Aksenov, N. D., Artamonova, T.O., Khodorkovskii, M.A., Alenina, N., Onichtchouk, D., Wu, G., Schöler, H.R. and Tomilin, A.N.
Abstract:	The transcription factor Oct4 plays a key regulatory role in the induction and maintenance of cellular pluripotency. With this paper, 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, TBP, 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. SIGNIFICANCE STATEMENT: In this work, the authors found that poly(C)-binding protein hnRNP-K occupy distal and proximal enhancers of the Oct4 gene via TC-elements. Genome-wide analysis revealed a lot of colocalizations of hnRNP-K with TBP, Oct4, Otx2 and active histone marks. A very intriguing aspect of the study is that hnRNP-K role expands to recruitment of the general transcription factor TBP to TATA-less genes.
Keywords:	Pluripotent Stem Cells, hnRNP-K, Oct4, Pou5f1, Chromatin, Histone Code, Animals, Mice
Source:	Stem Cells
ISSN:	1066-5099
Publisher:	Wiley
Volume:	37
Number:	8
Page Range:	1018-1029
Date:	August 2019
Official Publication:	https://doi.org/10.1002/stem.3025
PubMed:	View item in PubMed

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