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Functional interaction between PROX1, ERR[alpha] and PGC-1[alpha] in the control of energy metabolism

Nuclear receptors play crucial roles in the transcriptional regulation of many biological processes such as development and cellular differentiation. ERRalpha is known, along with coactivator PGC-1alpha, to playa central role in the control of energy metabolism in cardiac and skeletal muscle. They activate the expression of many genes involved in mitochondrial oxidative metabolism. Here we identified PROX1, a factor that was previously shown to broadly influence metabolism, as a regulator of this pathway. Indeed, PROX1 interacts in vitro and in vivo with both ERRalpha and PGC-1alpha. To provide more insight on the hepatic functions of ERRalpha and PROX1, we performed ChIP-on-chip using mouse liver, identifying a large number of ERRalpha and PROX1 genomic targets and reinforcing their role in energy metabolism. Over 40% of the target genes were found to be common to both factors and we observed that PROX1 could be recruited to ERRalpha binding sites and act as a negative regulator o fthe ERRalpha/POC-1alpha pathway.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111571
Date January 2009
CreatorsCharest-Marcotte, Alexis, 1984-
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Biochemistry.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 003135235, proquestno: AAIMR66873, Theses scanned by UMI/ProQuest.

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