hnRNP‐K Targets Open Chromatin in Mouse Embryonic Stem Cells in Concert with Multiple Regulators

• Published in: Stem cells (Dayton, Ohio) Vol. 37; no. 8; pp. 1018 - 1029
• Main Authors: 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., Alenina, Natalia, Onichtchouk, Daria, Wu, Guangming, Schöler, Hans R., Tomilin, Alexey N.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2019; Oxford University Press
• Subjects: Chromatin; Deoxyribonucleic acid; DNA; Embryo cells; Enhancers; Gene expression; Genomes; Histone code; hnRNP‐K; Maintenance; Oct-4 protein; Oct4; Otx2 protein; Pluripotency; Pluripotent stem cells; Pou5f1; Proteins; Regulators; Ribonucleic acid; RNA; Stem cell transplantation; Stem cells; Viability; Oct4; hnRNP-K; Chromatin; Pluripotent stem cells; Histone code; Pou5f1
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.3025

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 This picture illustrates that hnRNP‐K is localized exclusively within open chromatin, which is marked by H3K27ac, H3K9ac, and H3K4me3.