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
Publication Date
2004-05-15
Document Type
Article
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.
DOI of Published Version
10.1128/MCB.24.11.4651-4663.2004
Source
Mol Cell Biol. 2004 Jun;24(11):4651-63. Link to article on publisher's site
Journal/Book/Conference Title
Molecular and cellular biology
Related Resources
PubMed ID
15143161
Repository Citation
Salma N, Xiao H, Mueller E, Imbalzano AN. (2004). Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor. GSBS Student Publications. https://doi.org/10.1128/MCB.24.11.4651-4663.2004. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1071