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PMID: 19933152 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression.

Genes & development ·Vol. 23 ·No. 22 ·2009-11-15 ·Pages 2625-38

Savarese F, Dávila A, Nechanitzky R, De La Rosa-Velazquez I, Pereira CF, Engelke R, Takahashi K, Jenuwein T, Kohwi-Shigematsu T, Fisher AG, Grosschedl R

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 Nanog(high) 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.

MeSH Terms
Animals B-Lymphocytes/metabolism Cell Differentiation Cell Line Embryonic Stem Cells/cytology Gene Expression Regulation, Developmental Homeodomain Proteins/genetics Humans Kruppel-Like Factor 4 Matrix Attachment Region Binding Proteins/metabolism Mice Nanog Homeobox Protein Transcription Factors/metabolism
Chemicals
Homeodomain Proteins KLF4 protein, human Klf4 protein, mouse Kruppel-Like Factor 4 Matrix Attachment Region Binding Proteins NANOG protein, human Nanog Homeobox Protein Nanog protein, mouse SATB2 protein, mouse Satb1 protein, mouse Transcription Factors
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Savarese Fabio
Max Planck Institute of Immunobiology, Department of Cellular and Molecular Immunology, 79108 Freiburg, Germany.
Dávila Amparo
Nechanitzky Robert
De La Rosa-Velazquez Inti
Pereira Carlos F
Engelke Rudolf
Takahashi Keiko
Jenuwein Thomas
Kohwi-Shigematsu Terumi
Fisher Amanda G
Grosschedl Rudolf
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
1549-5477
DOI
10.1101/gad.1815709
Published
2009-11-15
Pages
2625-38
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC2779756
Subset
IM
Grants
Medical Research Council · MC_U120027516 · United Kingdom
External Links
PubMed source DOI: 10.1101/gad.1815709 PMC Full Text View journal details
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