Two human homologues ofSaccharomyces cerevisiae SWI2/SNF2andDrosophila brahmaare transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor

Abstract

A set of genes (SWI1, SWI2/SNF2, SWI3, SNF5 and SNF6) in Saccharomyces cerevisiae are required for transcription of a variety of yeast genes. It was recently reported that the mammalian glucocorticoid receptor failed to activate transcription when transiently expressed in swi1-, swi2- or swi3- yeast strains. We report here that two highly related human cDNAs, hSNF2 alpha and -beta, encode amino acid sequences homologous to both the yeast SWI2/SNF2 and the Drosophila brahma. Similar to their yeast and Drosophila counterparts, both human cDNAs contain helicase motifs, a bromodomain, a highly charged C-terminal sequence and an N-terminal sequence rich in proline, glutamine and glycine. Tissue distribution of the mRNAs varied slightly. Transcriptional activation by the estrogen receptor and the retinoic acid receptor was enhanced by co-expression of either hSNF2 cDNA. No enhancement was observed for promoters which do not respond to nuclear receptors. We suggest that global transcriptional coactivators equivalent to the yeast SWI/SNF complex exist in mammalian cells.

MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

“…BRG1 encodes one ATPase of the SWI/SNF chromatin remodeling complex and is involved in the transcriptional control of various cell processes, such as embryonic development and cell differentiation ( 23,24 ). Some of these activities also require the complex to interact with nuclear receptors ( 25 ). The functional relationship of MYC with BRG1 and with the SWI/SNF complex is well established.…”

The SWI/SNF complex and cancer

“…The ATPase domains of BRM and BRG1 are composed of helicase and DEAD box domains, which function as the motor units that convert ATP energy to mechanical movement (Muchardt and Yaniv, 1999a). These regions are highly conserved and show a high homology with both DEAD box proteins and helicase domain in other species (Chiba et al, 1994). Both BRG1 (210-345 aa) and BRM (255-375 aa) are highly enriched for proline residues, 35 and 21%, respectively, near their N termini.…”

Nuclear receptors and chromatin remodeling machinery

“…Many studies have utilized the MMTV promoter system to examine the role of the SWI/SNF remodeling complex in NRmediated transcription regulation and these observations may also be found for other NRresponsive genes. Estrogen receptor (ER) has been shown to require BRG1 activity for ERmediated transcriptional activity (Chiba et al, 1994;Muchardt and Yaniv, 1993). In BRG1-null cells, ERα-mediated transcriptional initiation of estrogen-responsive genes was diminished; however, upon BRG1 reintroduction, ER transcription activity was found to be restored.…”