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.
Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.111571 |
Date | January 2009 |
Creators | Charest-Marcotte, Alexis, 1984- |
Publisher | McGill University |
Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
Language | English |
Detected Language | English |
Type | Electronic Thesis or Dissertation |
Format | application/pdf |
Coverage | Master of Science (Department of Biochemistry.) |
Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
Relation | alephsysno: 003135235, proquestno: AAIMR66873, Theses scanned by UMI/ProQuest. |
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