Localized recruitment of a chromatin-remodeling activity by an activator in vivo drives transcriptional elongation

  1. Laura L. Corey1,2,
  2. Christine S. Weirich1,2,4,
  3. Ivor J. Benjamin3, and
  4. Robert E. Kingston1,2,5
  1. 1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; 2Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; 3Department of Internal Medicine and Division of Cell and Molecular Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA

Abstract

To understand the role of chromatin-remodeling activities in transcription, it is necessary to understand how they interact with transcriptional activators in vivo to regulate the different steps of transcription. Human heat shock factor 1 (HSF1) stimulates both transcriptional initiation and elongation. We replaced mouse HSF1 in fibroblasts with wild-type and mutant human HSF1 constructs and characterized regulation of an endogenous mouse hsp70 gene. A mutation that diminished transcriptional initiation led to twofold reductions in hsp70 mRNA induction and recruitment of a SWI/SNF remodeling complex. In contrast, a mutation that diminished transcriptional elongation abolished induction of full-length mRNA, SWI/SNF recruitment, and chromatin remodeling, but minimally impaired initiation from the hsp70 promoter. Another remodeling factor, SNF2h, is constitutively present at the promoter irrespective of the genotype of HSF1. These data suggest that localized recruitment of SWI/SNF drives a specialized remodeling reaction necessary for the production of full-length hsp70 mRNA.

Keywords

Footnotes

  • 4 Present address: Department of Molecular and Cell Biology, Division of Cell and Developmental Biology, University of California-Berkeley, Berkeley, CA 94720, USA.

  • Corresponding author.

  • 5 E-MAIL Kingston{at}molbio.mgh.harvard.edu; FAX (617) 726-5949.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1071803.

    • Accepted April 9, 2003.
    • Received December 31, 2002.
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