A novel SP1/SP3 dependent intronic enhancer governing transcription of the UCP3 gene in brown adipocytes

Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein implicated in lipid handling and metabolism of reactive oxygen species. Its transcription is mainly regulated by peroxisome proliferator-activated receptors (PPAR), a family of nuclear hormone receptors. Employing bandshift assays,...

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Published in:	PloS one 2013-12, Vol.8 (12), p.e83426-e83426
Main Authors:	Hoffmann, Christoph, Zimmermann, Anika, Hinney, Anke, Volckmar, Anna-Lena, Jarrett, Harry W, Fromme, Tobias, Klingenspor, Martin
Format:	Article
Language:	eng
Subjects:	Adipocytes Adipocytes, Brown - metabolism Animals Base Sequence Binding Binding Sites - genetics Biology Cell culture Cell Line Child & adolescent psychiatry Clonal deletion Cricetinae Data mining Data processing Deoxyribonucleic acid DNA DNA - genetics DNA - metabolism Enhancer Elements, Genetic Enzymes Event-related potentials Fatty acids Food Gene expression Gene Expression Regulation Gene Knockdown Techniques Genes Genetic aspects Genetic transcription Introns Ion Channels - genetics Ligands Lipid metabolism Lipids Medicine Membrane proteins Metabolism Mice Mitochondria Mitochondrial DNA Mitochondrial Proteins - genetics Models, Biological Molecular Sequence Data Musculoskeletal system MyoD protein MyoD Protein - metabolism Myogenin Myogenin - metabolism Nuclear receptors Nutrition Oxygen p300-CBP Transcription Factors - metabolism Peroxisome proliferator-activated receptors Phodopus Phodopus sungorus Physiological aspects PPAR gamma - agonists PPAR gamma - metabolism Protein Binding Protein turnover Proteins Psychotherapy Rats Reactive oxygen species Receptors Recruitment Reporter gene Ribonucleic acid RNA RNA-mediated interference Rodents Sp1 protein Sp1 Transcription Factor - antagonists & inhibitors Sp1 Transcription Factor - genetics Sp1 Transcription Factor - metabolism Sp3 Transcription Factor - antagonists & inhibitors Sp3 Transcription Factor - genetics Sp3 Transcription Factor - metabolism Thermogenesis Transcription Transcription (Genetics) Uncoupling Protein 3
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Summary:	Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein implicated in lipid handling and metabolism of reactive oxygen species. Its transcription is mainly regulated by peroxisome proliferator-activated receptors (PPAR), a family of nuclear hormone receptors. Employing bandshift assays, RNA interference and reporter gene assays we examine an intronic region in the UCP3 gene harboring a cis-element essential for expression in brown adipocytes. We demonstrate binding of SP1 and SP3 to this element which is adjacent to a direct repeat 1 element mediating activation of UCP3 expression by PPARγ agonists. Transactivation mediated by these elements is interdependent and indispensable for UCP3 expression. Systematic deletion uncovered a third binding element, a putative NF1 site, in close proximity to the SP1/3 and PPARγ binding elements. Data mining demonstrated binding of MyoD and Myogenin to this third element in C2C12 cells, and, furthermore, revealed recruitment of p300. Taken together, this intronic region is the main enhancer driving UCP3 expression with SP1/3 and PPARγ as the core factors required for expression.
ISSN:	1932-6203 1932-6203