INO80 facilitates pluripotency gene activation in embryonic stem cell self-renewal, reprogramming, and blastocyst development

Cell Stem Cell. 2014 May 1;14(5):575-91. doi: 10.1016/j.stem.2014.02.013.


The master transcription factors play integral roles in the pluripotency transcription circuitry of embryonic stem cells (ESCs). How they selectively activate expression of the pluripotency network while simultaneously repressing genes involved in differentiation is not fully understood. Here, we define a requirement for the INO80 complex, a SWI/SNF family chromatin remodeler, in ESC self-renewal, somatic cell reprogramming, and blastocyst development. We show that Ino80, the chromatin remodeling ATPase, co-occupies pluripotency gene promoters with the master transcription factors, and its occupancy is dependent on OCT4 and WDR5. At the pluripotency genes, Ino80 maintains an open chromatin architecture and licenses recruitment of Mediator and RNA polymerase II for gene activation. Our data reveal an essential role for INO80 in the expression of the pluripotency network and illustrate the coordination among chromatin remodeler, transcription factor, and histone-modifying enzyme in the regulation of the pluripotent state.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Blastocyst / cytology*
  • Blastocyst / metabolism
  • Cell Differentiation / physiology
  • Cell Line
  • Chromatin Assembly and Disassembly / genetics
  • Chromatin Assembly and Disassembly / physiology
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism*
  • Female
  • In Vitro Techniques
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Models, Biological
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Proteins / genetics
  • Proteins / metabolism


  • Intracellular Signaling Peptides and Proteins
  • Octamer Transcription Factor-3
  • Proteins
  • Wdr5 protein, mouse
  • DNA Helicases

Associated data

  • GEO/GSE49137