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

Item Type:Article
Title:hnRNP-K targets open chromatin in mouse embryonic stem cells in concert with multiple regulators
Creators Name:Bakhmet, E.I. and Nazarov, I.B. and Gazizova, A.R. and Vorobyeva, N.E. and Kuzmin, A.A. and Gordeev, M.N. and Sinenko, S.A. and Aksenov, N. D. and Artamonova, T.O. and Khodorkovskii, M.A. and Alenina, N. and Onichtchouk, D. and Wu, G. and 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
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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