Diversity and specialization of mammalian SWI/SNF complexes.
The SWI/SNF complex in yeast facilitates the function of transcriptional activators by opposing chromatin-dependent repression of transcription. We demonstrate that in mammals SWI/SNF complexes are present in multiple forms made up of 9-12 proteins that we refer to as BRG1-associated factors (BAFs) ranging from 47 to 250 kD. We have isolated cDNAs for human BAF155, BAF170, and BAF60. BAF155 and BAF170 are encoded by separate genes that are both homologs of yeast SWI3. Both contain a region of similarity to the DNA binding domain of myb, but lack the basic residues known to be necessary for interaction with DNA. The two SWI3 homologs copurify on antibody columns specific for either BAF155 or BAF170, indicating that they are in the same complex. BAF60 is encoded by a novel gene family. An open reading frame from yeast, which is highly homologous, encodes the previously uncharacterized 73-kD subunit of the yeast SWI/SNF complex required for transcriptional activation by the glucocorticoid receptor (Cairns et al., this issue). BAF60a is expressed in all tissues examined, whereas BAF60b and BAF60c are expressed preferentially in muscle and pancreas, respectively. BAF60a is present within the 2000-kD BRG1 complex, whereas BAF60b is in a distinct complex that shares some but not all subunits with the BRG1 complex. The observed similarity between mammalian BAF190, BAF170, BAF155, BAF60, and BAF47 and yeast SNF2/SWI2, SWI3, SWI3, SWP73, and SNF5, respectively, underscores the similarity of the mammalian and yeast complexes. However, the complexes in mammals are more diverse than the SWI/SNF complex in yeast and are likely dedicated to developmentally distinct functions.
Wang
W
W
Howard Hughes Medical Institute, Department of Developmental Biology, Stanford University, California 94305-5428, USA.
Xue
Y
Y
Zhou
S
S
Kuo
A
A
Cairns
B R
BR
Crabtree
G R
GR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002843:Chromatin / Q000502:physiology; D003001:Cloning, Molecular; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D005800:Genes, Fungal; D006801:Humans; D007624:KB Cells; D008969:Molecular Sequence Data; D005810:Multigene Family; D009132:Muscles / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics*; D009857:Oncogenes; D010179:Pancreas / Q000378:metabolism; D016601:RNA-Binding Proteins; D016364:Reading Frames; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C101681:SMARCC1 protein, human; C101682:SMARCC2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C089969:snf protein, Drosophila; C084108:SMARCA4 protein, human; D004265:DNA Helicases