Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression.
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.
Savarese
Fabio
F
Max Planck Institute of Immunobiology, Department of Cellular and Molecular Immunology, 79108 Freiburg, Germany.
Dávila
Amparo
A
Nechanitzky
Robert
R
De La Rosa-Velazquez
Inti
I
Pereira
Carlos F
CF
Engelke
Rudolf
R
Takahashi
Keiko
K
Jenuwein
Thomas
T
Kohwi-Shigematsu
Terumi
T
Fisher
Amanda G
AG
Grosschedl
Rudolf
R
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D000071317:Nanog Homeobox Protein; D014157:Transcription Factors / Q000378:metabolism*
D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D036961:Matrix Attachment Region Binding Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C501473:SATB2 protein, mouse; C469541:Satb1 protein, mouse; D014157:Transcription Factors