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 rel ated human cDNAs, hSNF2 alpha and -beta, encode amino acid sequences h omologous to both the yeast SW12/SNF2 and the Drosophila brahma. Simil ar to their yeast and Drosophila counterparts, both human cDNAs contai n helicase motifs, a bromodomain, a highly charged C-terminal sequence and an N-terminaI sequence rich in proline, glutamine and glycine. Ti ssue distribution of the mRNAs varied slightly. Transcriptional activa tion by the estrogen receptor and the retinoic acid receptor was enhan ced by co-expression of either hSNF2 cDNA. No enhancement was observed for promoters which do not respond to nuclear receptors. We suggest t hat global transcriptional coactivators equivalent to the yeast SWI/SN F complex exist in mammalian cells.