Mechanisms of OCT4-SOX2 motif readout on nucleosomes

Science. 2020 Jun 26;368(6498):1460-1465. doi: 10.1126/science.abb0074. Epub 2020 Apr 23.


Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo-electron microscopy at two preferred positions. Depending on motif location, OCT4 and SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from histone H2A and histone H3; however, at an inverted motif, the TFs only induce local DNA distortions. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures, reading out a partial motif. These findings explain site-specific nucleosome engagement by the pluripotency factors OCT4 and SOX2, and they reveal how TFs distort nucleosomes to access chromatinized motifs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cryoelectron Microscopy
  • DNA / chemistry
  • Gene Expression Regulation*
  • Histones / chemistry
  • Mice
  • Mouse Embryonic Stem Cells / metabolism
  • Nucleosomes / chemistry*
  • Octamer Transcription Factor-3 / chemistry*
  • SOXB1 Transcription Factors / chemistry*


  • Histones
  • Nucleosomes
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse
  • DNA