Dissecting the role of distinct OCT4-SOX2 heterodimer configurations in pluripotency

Sci Rep. 2015 Aug 28;5:13533. doi: 10.1038/srep13533.

Abstract

The transcription factors OCT4 and SOX2 are required for generating induced pluripotent stem cells (iPSCs) and for maintaining embryonic stem cells (ESCs). OCT4 and SOX2 associate and bind to DNA in different configurations depending on the arrangement of their individual DNA binding elements. Here we have investigated the role of the different OCT4-SOX2-DNA assemblies in regulating and inducing pluripotency. To this end, we have generated SOX2 mutants that interfere with specific OCT4-SOX2 heterodimer configurations and assessed their ability to generate iPSCs and to rescue ESC self-renewal. Our results demonstrate that the OCT4-SOX2 configuration that dimerizes on a Hoxb1-like composite, a canonical element with juxtaposed individual binding sites, plays a more critical role in the induction and maintenance of pluripotency than any other OCT4-SOX2 configuration. Overall, the results of this study provide new insight into the protein interactions required to establish a de novo pluripotent network and to maintain a true pluripotent cell fate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cellular Reprogramming
  • Human Embryonic Stem Cells
  • Humans
  • Mice, Transgenic
  • Models, Molecular
  • Octamer Transcription Factor-3 / metabolism*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Protein Multimerization*
  • SOXB1 Transcription Factors / metabolism*

Substances

  • Octamer Transcription Factor-3
  • SOXB1 Transcription Factors