GSBS Student Publications

Title

Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

5-15-2004

Document Type

Article

Medical Subject Headings

Adipose Tissue; *Cell Differentiation; Chromosomal Proteins, Non-Histone; Enzymes; Fibroblasts; Humans; Promoter Regions (Genetics); Receptors, Cytoplasmic and Nuclear; Transcription Factor TFIIH; Transcription Factors; Transcription Factors, TFII

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The peroxisome proliferator-activated receptor gamma (PPARgamma) regulates adipogenesis, lipid metabolism, and glucose homeostasis, and roles have emerged for this receptor in the pathogenesis and treatment of diabetes, atherosclerosis, and cancer. We report here that induction of the PPARgamma activator and adipogenesis forced by overexpression of adipogenic regulatory proteins is blocked upon expression of dominant-negative BRG1 or hBRM, the ATPase subunits of distinct SWI/SNF chromatin-remodeling enzymes. We demonstrate that histone hyperacetylation and the binding of C/EBP activators, polymerase II (Pol II), and general transcription factors (GTFs) initially occurred at the inducible PPARgamma2 promoter in the absence of SWI/SNF function. However, the polymerase and GTFs were subsequently lost from the promoter in cells expressing dominant-negative SWI/SNF, explaining the inhibition of PPARgamma2 expression. To corroborate these data, we analyzed interactions at the PPARgamma2 promoter in differentiating preadipocytes. Changes in promoter structure, histone hyperacetylation, and binding of C/EBP activators, Pol II, and most GTFs preceded the interaction of SWI/SNF enzymes with the PPARgamma2 promoter. However, transcription of the PPARgamma2 gene occurred only upon subsequent association of SWI/SNF and TFIIH with the promoter. Thus, induction of the PPARgamma nuclear hormone receptor during adipogenesis requires SWI/SNF enzymes to facilitate preinitiation complex function.

Rights and Permissions

Citation: Mol Cell Biol. 2004 Jun;24(11):4651-63. Link to article on publisher's site

DOI of Published Version

10.1128/MCB.24.11.4651-4663.2004

Related Resources

Link to Article in PubMed

Journal Title

Molecular and cellular biology

PubMed ID

15143161