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

Results of this study showed that the poly(C)-binding protein hnRNP-K occupies in embryonic stem cells (ESCs) both distal and proximal enhancers of the Oct4 gene via CT-rich elements. Genome-wide analysis revealed many colocalizations of hnRNP-K with TATA-box binding protein (TBP), Oct4, Otx2, and active histone marks. Also, comparison of hnRNP-K ChIP-seq data with MNase-seq and ATAC-seq revealed that this protein exclusively targets open chromatin of ESCs.