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Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression

Savarese, Fabio; Dávila, Amparo; Nechanitzky, Robert; De La Rosa-Velazquez, Inti; Pereira, Carlos F. LU ; Engelke, Rudolf; Takahashi, Keiko; Jenuwein, Thomas; Kohwi-Shigematsu, Terumi and Fisher, Amanda G., et al. (2009) In Genes and Development 23(22). p.2625-2638
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... (More)

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.

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type
Contribution to journal
publication status
published
keywords
Differentiation, Embryonic stem cells, Nanog, Pluripotency, Satb1, Satb2
in
Genes and Development
volume
23
issue
22
pages
14 pages
publisher
Cold Spring Harbor Laboratory Press
external identifiers
  • scopus:72749087503
ISSN
0890-9369
DOI
10.1101/gad.1815709
language
English
LU publication?
no
id
b2366f91-393b-4eaa-9005-caecae311bc6
date added to LUP
2017-10-02 17:32:23
date last changed
2017-10-13 09:23:21
@article{b2366f91-393b-4eaa-9005-caecae311bc6,
  abstract     = {<p>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<sup>-/-</sup> 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 <sup>-/-</sup> cultures have a higher proportion of Nanog<sup>high</sup> 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<sup>-/-</sup>Satb2<sup>-/-</sup> 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.</p>},
  author       = {Savarese, Fabio and Dávila, Amparo and Nechanitzky, Robert and De La Rosa-Velazquez, Inti and Pereira, Carlos F. and Engelke, Rudolf and Takahashi, Keiko and Jenuwein, Thomas and Kohwi-Shigematsu, Terumi and Fisher, Amanda G. and Grosschedl, Rudolf},
  issn         = {0890-9369},
  keyword      = {Differentiation,Embryonic stem cells,Nanog,Pluripotency,Satb1,Satb2},
  language     = {eng},
  month        = {11},
  number       = {22},
  pages        = {2625--2638},
  publisher    = {Cold Spring Harbor Laboratory Press},
  series       = {Genes and Development},
  title        = {Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression},
  url          = {http://dx.doi.org/10.1101/gad.1815709},
  volume       = {23},
  year         = {2009},
}