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


  • E.I. Bakhmet
  • I.B. Nazarov
  • A.R. Gazizova
  • N.E. Vorobyeva
  • A.A. Kuzmin
  • M.N. Gordeev
  • S.A. Sinenko
  • N. D. Aksenov
  • T.O. Artamonova
  • M.A. Khodorkovskii
  • N. Alenina
  • D. Onichtchouk
  • G. Wu
  • H.R. Schöler
  • A.N. Tomilin


  • Stem Cells


  • Stem Cells 37 (8): 1018-1029


  • 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.