Open AccesshnRNP‐K Targets Open Chromatin in Mouse Embryonic Stem Cells in Concert with Multiple Regulators
Author(s) -
Bakhmet Evgeny I.,
Nazarov Igor B.,
Gazizova Adel R.,
Vorobyeva Nadezhda E.,
Kuzmin Andrey A.,
Gordeev Mikhail N.,
Sinenko Sergey A.,
Aksenov Nikolai D.,
Artamonova Tatyana O.,
Khodorkovskii Mikhail A.,
Alenitalia,
Onichtchouk Daria,
Wu Guangming,
Schöler Hans R.,
Tomilin Alexey N.
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3025
Subject(s) - biology , homeobox protein nanog , sox2 , chromatin , embryonic stem cell , microbiology and biotechnology , transcription factor , nanog homeobox protein , enhancer , stem cell , histone , genetics , induced pluripotent stem cell , gene
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. Stem Cells 2019;37:1018–1029