DNA bending is induced by binding of the peroxisome proliferator-activated receptor gamma 2 heterodimer to its response element in the murine lipoprotein lipase promoter

Biochemical and Biophysical Research Communications
C E RobinsonJ M Gimble

Abstract

The peroxisome proliferator activated receptor gamma 2 (PPAR gamma 2) is a critical transcriptional regulator of adipogenesis. Lipoprotein lipase is one of the earliest genes induced following exposure of pre-adipocytes to PPAR gamma 2 ligands such as the thiazolidinediones. A unique PPAR gamma 2 DNA recognition element was mapped to the region between -171 to -149 bp of the murine LPL promoter, based on transfection analysis of deletion constructs and gel retention assays using bacterially expressed, affinity purified recombinant proteins. Circular permutation analysis determined that binding of the PPAR gamma 2/retinoic acid X receptor (RXR) heterodimer to its LPL promoter recognition element induced DNA bending at an angle of approximately 46 degrees. Parallel studies using an optimal PPAR recognition element obtained a comparable bending angle of 56 degrees. This is the first demonstration that binding of a PPAR protein to its recognition element causes a distortion of the DNA configuration. It indicates that PPAR gamma 2 utilizes a common mechanism shared by other nuclear hormone receptor proteins reported to induce bending at their DNA binding sites.

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Citations

Nov 5, 2008·Genes & Development·Martina I LefterovaMitchell A Lazar
Sep 13, 2016·Biochimica Et Biophysica Acta·Ortal Amber-VitosYossi Tsfadia
May 16, 2002·The Journal of Biological Chemistry·Philippa MelamedChoy Hew
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Jun 2, 2006·Clinical Science·Thais Martins de LimaRui Curi
Nov 18, 2000·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Y TakahashiH Fujita
Jul 17, 1999·European Journal of Pharmacology·T ShibataK Wakitani

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