GSBS Student Publications

Student Author(s)

Cynthia J. Guidi

GSBS Program

Cell Biology

UMMS Affiliation

Department of Cell Biology

Date

3-25-2000

Document Type

Article

Medical Subject Headings

3T3 Cells; Animals; Chromatin; *Gene Expression Regulation; HSP70 Heat-Shock Proteins; Mice; Nuclear Proteins; Signal Transduction; Transcription Factors

Disciplines

Cell Biology | Life Sciences | Medicine and Health Sciences

Abstract

ATP-dependent chromatin-remodeling complexes are conserved among all eukaryotes and function by altering nucleosome structure to allow cellular regulatory factors access to the DNA. Mammalian SWI-SNF complexes contain either of two highly conserved ATPase subunits: BRG1 or BRM. To identify cellular genes that require mammalian SWI-SNF complexes for the activation of gene expression, we have generated cell lines that inducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP. The mutant subunits physically associate with at least two endogenous members of mammalian SWI-SNF complexes, suggesting that nonfunctional, dominant negative complexes may be formed. We determined that expression of the mutant BRG1 or BRM proteins impaired the ability of cells to activate the endogenous stress response gene hsp70 in response to arsenite, a metabolic inhibitor, or cadmium, a heavy metal. Activation of hsp70 by heat stress, however, was unaffected. Activation of the heme oxygenase 1 promoter by arsenite or cadmium and activation of the cadmium-inducible metallothionein promoter also were unaffected by the expression of mutant SWI-SNF components. Analysis of a subset of constitutively expressed genes revealed no or minimal effects on transcript levels. We propose that the requirement for mammalian SWI-SNF complexes in gene activation events will be specific to individual genes and signaling pathways.

Rights and Permissions

Citation: Mol Cell Biol. 2000 Apr;20(8):2839-51. Link to article on publisher's website

Related Resources

Link to article in PubMed

Journal Title

Molecular and cellular biology

PubMed ID

10733587

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