Functional selectivity of recombinant mammalian SWI/SNF subunits

• Published in: Genes & development 2000-10, Vol.14 (19), p.2441-2451
• Main Authors: Kadam, S, McAlpine, G S, Phelan, M L, Kingston, R E, Jones, K A, Emerson, B M
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Binding Sites; Chromatin - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; DNA Helicases; DNA-Binding Proteins - metabolism; EKLF protein; Erythroid-Specific DNA-Binding Factors; Globins - genetics; HIV-1 - genetics; Kruppel-Like Transcription Factors; Models, Genetic; NF-kappa B - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nucleosomes - metabolism; Promoter Regions, Genetic; Protein Binding; Protein Subunits; Recombinant Proteins - metabolism; Research Paper; SWI/SNF complex; Transcription Factors - metabolism; Transcriptional Activation; Zinc Fingers
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.828000

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.