Oct4 links multiple epigenetic pathways to the pluripotency network

Cell Res. 2012 Jan;22(1):155-67. doi: 10.1038/cr.2011.179. Epub 2011 Nov 15.

Abstract

Oct4 is a well-known transcription factor that plays fundamental roles in stem cell self-renewal, pluripotency, and somatic cell reprogramming. However, limited information is available on Oct4-associated protein complexes and their intrinsic protein-protein interactions that dictate Oct4's critical regulatory activities. Here we employed an improved affinity purification approach combined with mass spectrometry to purify Oct4 protein complexes in mouse embryonic stem cells (mESCs), and discovered many novel Oct4 partners important for self-renewal and pluripotency of mESCs. Notably, we found that Oct4 is associated with multiple chromatin-modifying complexes with documented as well as newly proved functional significance in stem cell maintenance and somatic cell reprogramming. Our study establishes a solid biochemical basis for genetic and epigenetic regulation of stem cell pluripotency and provides a framework for exploring alternative factor-based reprogramming strategies.

Publication types

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

MeSH terms

  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cellular Reprogramming
  • Chromatography, Affinity
  • Electrophoresis, Polyacrylamide Gel
  • Embryonic Stem Cells / chemistry
  • Embryonic Stem Cells / cytology
  • Epigenesis, Genetic*
  • Mass Spectrometry / methods
  • Mice
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / isolation & purification*
  • Octamer Transcription Factor-3 / chemistry
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / isolation & purification*
  • Pluripotent Stem Cells / chemistry
  • Pluripotent Stem Cells / cytology*
  • Protein Interaction Mapping / methods*
  • SOXB1 Transcription Factors / chemistry

Substances

  • Multiprotein Complexes
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse