Targeting of SWI/SNF chromatin remodelling complexes to estrogen-responsive genes

Abstract

SWI/SNF complexes are ATP-dependent chromatin remodelling enzymes that have been implicated in the regulation of gene expression in yeast and higher eukaryotes. BRG1, a catalytic subunit in the mammalian SWI/SNF complex, is required for transcriptional activation by the estrogen receptor, but the mechanisms by which the complex is recruited to estrogen target genes are unknown. Here, we have identi®ed an interaction between the estrogen receptor and BAF57, a subunit present only in mammalian SWI/SNF complexes, which is stimulated by estrogen and requires both a functional hormone-binding domain and the DNA-binding region of the receptor. We also found an additional interaction between the p160 family of coactivators and BAF57 and demonstrate that the ability of p160 coactivators to potentiate transcription by the estrogen receptor is dependent on BAF57 in transfected cells. Moreover, chromatin immunoprecipitation assays demonstrated that BAF57 is recruited to the estrogen-responsive promoter, pS2, in a liganddependent manner. These results suggest that one of the mechanisms for recruiting SWI/SNF complexes to estrogen target genes is by means of BAF57.

The SWI/SNF complex and cancer

“…BAF57 binds to and is required for both estrogen and androgen receptor function (Belandia et al, 2002;Link et al, 2005). Preliminary data suggest that BAF57 may also regulate estrogen receptor expression (unpublished data), but the expression of BAF57 in primary tumors has not yet been investigated and the role of BAF57 in the etiology of ER-negative breast cancer remains to be determined.…”

“…The oncogenic transcription heterodimer activated protein-1 (AP-1) is known to be SWI/SNF dependent ; similarly, EKLF, which regulates b-hemogloblin synthesis, also requires this complex for its function (Armstrong et al, 1998;Lee et al, 1999). All known steroid receptors are functionally linked to SWI/SNF (Yoshinaga et al, 1992;Sumi-Ichinose et al, 1997;Fryer and Archer, 1998;Belandia et al, 2002;Inoue et al, 2002;Marshall et al, 2003;Flajollet et al, 2007). SWI/SNF has been linked to CD44, CEACAM1, E-cadherin and various integrins (Liu et al, 2001;Hendricks et al, 2004;Hill et al, 2004).…”

FIZ1 is expressed during photoreceptor maturation, and synergizes with NRL and CRX at rod-specific promoters in vitro

“…(Cheng, et al, 2004, Haider, et al, 2000 Nuclear receptors, as a family, are noted for both repression and activation effects that are mediated through Znfinger proteins. (Belandia, et al, 2002) Recent studies also indicate that the interaction of NR2E3 with NRL or CRX may not be direct and additional transcriptional regulatory proteins might be necessary for the formation of a stable complex in vivo. Appearance of FIZ1 during retinal maturation is consistent with our hypothesis that FIZ1 is required for the precise regulation of genes imparting cell-specific functionality.…”

Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt

“…Chromatin immunoprecipitation experiments have demonstrated the presence of hSWI/SNF components on the promoters of IFNgand IFNa-inducible genes, as well as on the IFNb promoter (Agalioti et al, 2000;Huang et al, 2002;Liu et al, 2002;Pattenden et al, 2002;Cui et al, 2004). hSWI/SNF is also present on the CD44 and E-cadherin promoters (Banine et al, 2005;Gresh et al, 2005), on the promoters for myogenin and muscle creatine kinase (Simone et al, 2004), and on steroid receptor targets (Fryer and Archer, 1998;DiRenzo et al, 2000;Belandia et al, 2002;Me´tivier et al, 2003;Link et al, 2005). Despite the growing knowledge of promoters regulated by hSWI/SNF, it is not well understood how the complex becomes localized and activated at various promoters; however, there is evidence for the involvement of signaling pathways.…”

“…The chromatin remodeling ability of hSWI/SNF has been shown to respond to various signaling pathways, including response to phosphoinositols (Zhao et al, 1998;Rando et al, 2002), the p38 pathway during skeletal myogenesis (Simone et al, 2004), interferons (Agalioti et al, 2000;Huang et al, 2002;Liu et al, 2002;Cui et al, 2004) and nuclear hormone receptors (Fryer and Archer, 1998;DiRenzo et al, 2000;Belandia et al, 2002;Me´tivier et al, 2003;Link et al, 2005). Phosphatidyl inositol 4,5-bisphosphate (PIP 2 ) has been shown to help increase the association of the SWI/SNF complex with the nuclear matrix (Zhao et al, 1998;Rando et al, 2002).…”