Satb1 and Satb2 regulate embryonic stem cell differentiation and Nanog expression

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.

The Sympathetic Neurotransmitter Switch Depends on the Nuclear Matrix Protein Satb2

“…Previous studies have shown that Satb2 interacts with different AT-rich DNA sequences, part of MARs/SARs (scaffold attachment regions), and is capable of either activating or repressing the transcription of the corresponding gene loci (Dobreva et al, 2003(Dobreva et al, , 2006Alcamo et al, 2008;Britanova et al, 2008;Savarese et al, 2009 (Fig. 4 A).…”

The AT-rich DNA-binding Protein SATB2 Promotes Expression and Physical Association of Human γ- and γ-Globin Genes

“…A recent study on the Nanog locus showed that both SATB2 and SATB1 regulated Nanog gene expression (7). We have previously shown that SATB1 interference in K562 cells also mildly decreases ␥-globin gene expression and the association between LCR and ␥-globin promoter (14), furthermore, the type III deacetylase SIRT, which deacetylates SATB1 in erythroid cells, also affects ␥-globin gene expression (16), whereas ChIP and ChIP-3C assays failed to confirm close connection of SATB1 to ␥-globin gene (14).…”

“…Notably, the MAR-binding protein SATB2, a homolog of SATB1, was also found to bind MAR-G ␥-pro. SATB2 has been reported to bind AT-rich regulatory elements for cell type-specific transcriptional regulation in pre-B cells, osteoblasts, brain, and embryonic stem (ES) cells (5)(6)(7)25). However, the regulatory roles of SATB2 in erythroid cells have not been investigated.…”

“…A study using knock-out mice showed that SATB2 regulates osteoblast function by modulating osteoblast-specific Runx2, ATF4 and several Hox genes (6). Although many genes that are targeted by SATB2 have been identified (5)(6)(7), the working mechanism of SATB2 in regulating target genes transcription has been largely unexplored.…”

Transcription factor and bone marrow stromal cells in osseointegration of dental implants

“…However, we recently found that SATB2 upregulates Osx expression independent of Runx2, but synergistically enhanced the regulatory effect of Runx2 on Osx promoter . Additionally, SATB2 plays an important role in embryonic stem (ES) cell pluripotency (Savarese et al, 2009). It has also been reported that Osterix (Osx) is an upstream regulator of SATB2 and can activate the SATB2 promoter reporter in a dose-dependent manner during bone formation (Tang et al, 2011).…”