The homeobox protein Prox1 is a negative modulator of ERRα/PGC- 1α bioenergetic functions

Alexis Charest-Marcotte, Catherine R. Dufour, Brian J. Wilson, Annie M. Tremblay, Lillian J. Eichner, Daniel H. Arlow, Vamsi K. Mootha, Vincent Giguère*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Estrogen-related receptor α (ERRα) and proliferatoractivated receptor γ coactivator-1α (PGC-1α) play central roles in the transcriptional control of energy homeostasis, but little is known about factors regulating their activity. Here we identified the homeobox protein prospero-related homeobox 1 (Prox1) as one such factor. Prox1 interacts with ERRa and PGC-1α, occupies promoters of metabolic genes on a genome-wide scale, and inhibits the activity of the ERRα/PGC-1α complex. DNA motif analysis suggests that Prox1 interacts with the genome through tethering to ERRα and other factors. Importantly, ablation of Prox1 and ERRα have opposite effects on the respiratory capacity of liver cells, revealing an unexpected role for Prox1 in the control of energy homeostasis.

Original languageEnglish (US)
Pages (from-to)537-542
Number of pages6
JournalGenes and Development
Volume24
Issue number6
DOIs
StatePublished - Mar 15 2010
Externally publishedYes

Keywords

  • ChIP-on-chip
  • Homeobox
  • Mitochondrial respiration
  • Nuclear receptor
  • Regulon

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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