Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression

Research output: Contribution to journalArticle

Abstract

Satb1 and the closely related Satb2 proteins regulate gene expression and higher-order chromatin structure of multigene clusters in vivo. In examining the role of Satb proteins in murine embryonic stem (ES) cells, we find that Satb1-/- cells display an impaired differentiation potential and augmented expression of the pluripotency determinants Nanog, Klf4, and Tbx3. Metastable states of self-renewal and differentiation competence have been attributed to heterogeneity of ES cells in the expression of Nanog. Satb1 -/- cultures have a higher proportion of Nanoghigh cells, and an increased potential to reprogram human B lymphocytes in cell fusion experiments. Moreover, Satb1-deficient ES cells show an increased expression of Satb2, and we find that forced Satb2 expression in wild-type ES cells antagonizes differentiation-associated silencing of Nanog and enhances the induction of NANOG in cell fusions with human B lymphocytes. An antagonistic function of Satb1 and Satb2 is also supported by the almost normal differentiation potential of Satb1-/-Satb2-/- ES cells. Taken together with the finding that both Satb1 and Satb2 bind the Nanog locus in vivo, our data suggest that the balance of Satb1 and Satb2 contributes to the plasticity of Nanog expression and ES cell pluripotency.

Details

Authors
  • Fabio Savarese
  • Amparo Dávila
  • Robert Nechanitzky
  • Inti De La Rosa-Velazquez
  • Carlos F. Pereira
  • Rudolf Engelke
  • Keiko Takahashi
  • Thomas Jenuwein
  • Terumi Kohwi-Shigematsu
  • Amanda G. Fisher
  • Rudolf Grosschedl
External organisations
  • Max Planck Institute of Immunobiology and Epigenetics
  • Imperial College London
  • University of California, Berkeley
Research areas and keywords

Keywords

  • Differentiation, Embryonic stem cells, Nanog, Pluripotency, Satb1, Satb2
Original languageEnglish
Pages (from-to)2625-2638
Number of pages14
JournalGenes and Development
Volume23
Issue number22
Publication statusPublished - 2009 Nov 15
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes