2 HUMAN HOMOLOGS OF SACCHAROMYCES-CEREVISIAE SW12/SNF2 AND DROSOPHILA-BRAHMA ARE TRANSCRIPTIONAL COACTIVATORS COOPERATING WITH THE ESTROGEN-RECEPTOR AND THE RETINOIC ACID RECEPTOR

A set of genes (SWI1, SW12/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 SW12/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-terminaI 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.