Transcriptional Activation by Oct4 Is Sufficient for the Maintenance and Induction of Pluripotency

Cell Rep. 2012 Feb 23;1(2):99-109. doi: 10.1016/j.celrep.2011.12.002. Epub 2012 Feb 16.

Abstract

Oct4 is an essential regulator of pluripotency in vivo and in vitro in embryonic stem cells, as well as a key mediator of the reprogramming of somatic cells into induced pluripotent stem cells. It is not known whether activation and/or repression of specific genes by Oct4 is relevant to these functions. Here, we show that fusion proteins containing the coding sequence of Oct4 or Xlpou91 (the Xenopus homolog of Oct4) fused to activating regions, but not those fused to repressing regions, behave as Oct4, suppressing differentiation and promoting maintenance of undifferentiated phenotypes in vivo and in vitro. An Oct4 activation domain fusion supported embryonic stem cell self-renewal in vitro at lower concentrations than that required for Oct4 while alleviating the ordinary requirement for the cytokine LIF. At still lower levels of the fusion, LIF dependence was restored. We conclude that the necessary and sufficient function of Oct4 in promoting pluripotency is to activate specific target genes.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • DNA / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism*
  • Leukemia Inhibitory Factor / pharmacology
  • Mice
  • Mutation / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Protein Binding / drug effects
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism
  • Transcriptional Activation* / drug effects
  • Xenopus

Substances

  • Leukemia Inhibitory Factor
  • Octamer Transcription Factor-3
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • DNA

Associated data

  • GEO/GSE24563