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

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. © AlphaMed Press 2019.