hnRNP-K targets open chromatin in mouse embryonic stem cells in concert with multiple regulators
Bakhmet EI, Nazarov IB, Gazizova AR, Vorobyeva NE, Kuzmin AA, Gordeev MN, Sinenko SA, Aksenov ND, Artamonova TO, Khodorkovskii MA, Alenina N, Onichtchouk D, Wu G, Schöler HR, Tomilin AN.
The transcription factor Oct4 plays a key regulatory role in the induction and maintenance of cel-lular pluripotency. With this paper, we show that ubiquitous and multifunctional poly(C)DNA/RNA-binding protein hnRNP-K occupiesOct4(Pou5f1) enhancers in embryonic stem cells(ESCs) but is dispensable for the initiation, maintenance, and downregulation ofOct4geneexpression. Nevertheless, hnRNP-K has an essential cell-autonomous function in ESCs to main-tain their proliferation and viability. To better understand mechanisms of hnRNP-K action in ESCswe have performed ChIP-seq analysis of genome-wide binding of hnRNP-K and identified severalthousands 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. Further-more, hnRNP-K localizes exclusively within open chromatin, implying its role in the onset and/ormaintenance of this chromatin state.
