title: Functional selectivity of recombinant mammalian SWI/SNF subunits.
abstract: The SWI/SNF family of chromatin-remodeling complexes plays a key role in facilitating the binding of specific transcription factors to nucleosomal DNA in diverse organisms from yeast to man. Yet the process by which SWI/SNF and other chromatin-remodeling complexes activate specific subsets of genes is poorly understood. We show that mammalian SWI/SNF regulates transcription from chromatin-assembled genes in a factor-specific manner in vitro. The DNA-binding domains (DBDs) of several zinc finger proteins, including EKLF, interact directly with SWI/SNF to generate DNase I hypersensitivity within the chromatin-assembled beta-globin promoter. Interestingly, we find that two SWI/SNF subunits (BRG1 and BAF155) are necessary and sufficient for targeted chromatin remodeling and transcriptional activation by EKLF in vitro. Remodeling is achieved with only the BRG1-BAF155 minimal complex and the EKLF zinc finger DBD, whereas transcription requires, in addition, an activation domain. In contrast, the BRG1-BAF155 complex does not interact or function with two unrelated transcription factors, TFE3 and NF-kappaB. We conclude that specific domains of certain transcription factors differentially target SWI/SNF complexes to chromatin in a gene-selective manner and that individual SWI/SNF subunits play unique roles in transcription factor-directed nucleosome remodeling.
authors.affiliation: Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kadam
authors.forename: G S
authors.initials: GS
authors.lastname: McAlpine
authors.forename: M L
authors.initials: ML
authors.lastname: Phelan
authors.forename: R E
authors.initials: RE
authors.lastname: Kingston
authors.forename: K A
authors.initials: KA
authors.lastname: Jones
authors.forename: B M
authors.initials: BM
authors.lastname: Emerson
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D016335:Zinc Fingers
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; D009707:Nucleosomes; D021122:Protein Subunits; D011994:Recombinant Proteins; C101681:SMARCC1 protein, human; C069203:TFE3 protein, human; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D005914:Globins; D000251:Adenosine Triphosphatases; D004265:DNA Helicases