OCT4 cooperates with distinct ATP-dependent chromatin remodelers in naïve and primed pluripotent states in human

Nat Commun. 2021 Aug 26;12(1):5123. doi: 10.1038/s41467-021-25107-3.


Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes. In naïve hESCs, OCT4 is associated with both BRG1 and BRM, the two paralog ATPases of the BAF complex. Genome-wide location analyses and genetic studies reveal that these two enzymes cooperate in a functionally redundant manner in the transcriptional regulation of blastocyst-specific genes. In contrast, in primed hESCs, OCT4 cooperates with BRG1 and SOX2 to promote chromatin accessibility at ectodermal genes. This work reveals how a common transcription factor utilizes differential BAF complexes to control distinct transcriptional programs in naïve and primed hESCs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Chromatin / genetics
  • Chromatin / metabolism*
  • Chromatin Assembly and Disassembly
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Embryonic Stem Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Protein Binding
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Chromatin
  • Nuclear Proteins
  • Nucleosomes
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Transcription Factors
  • Adenosine Triphosphate
  • SMARCA4 protein, human
  • DNA Helicases