Functional selectivity of recombinant mammalian SWI/SNF subunits

Shilpa Kadam, Glenn S. McAlpine, Michael L. Phelan, Robert E. Kingston, Katherine A. Jones, Beverly M. Emerson

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

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 β-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-κB. 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.

Original languageEnglish (US)
Pages (from-to)2441-2451
Number of pages11
JournalGenes and Development
Volume14
Issue number19
DOIs
StatePublished - Oct 1 2000
Externally publishedYes

Keywords

  • Chromatin
  • EKLF
  • SWI/SNF
  • Transcription
  • Zinc fingers
  • β-globin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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