Two human homologues of Saccharomyces cerevisiae SWI2/SNF2 and Drosophila brahma are transcriptional coactivators cooperating with the estrogen receptor and the retinoic acid receptor.
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.
Chiba
H
H
Department of Microbiology, Institute of Medical Science, University of Tokyo, Japan.
Muramatsu
M
M
Nomoto
A
A
Kato
H
H
D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005333:Fetus / Q000737:chemistry; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation / Q000235:genetics*; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C086469:brm protein, Drosophila; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; C499333:SNF2 protein, S cerevisiae; D004265:DNA Helicases