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

  1. Vincent Giguère1,2,6,7,8
  1. 1Goodman Cancer Centre, McGill University, Montréal, Québec H3A 1A3, Canada;
  2. 2Department of Biochemistry, McGill University, Montréal, Québec H3G 1Y6, Canada;
  3. 3Department of Systems Biology, Massachusetts General Hospital, Cambridge, Massachusetts 02142, USA;
  4. 4Centre for Human Genetic Research, Massachusetts General Hospital, Cambridge, Massachusetts 02142, USA;
  5. 5Broad Institute of Massachusetts Institute of Technology/Harvard, Cambridge, Massachusetts 02142, USA;
  6. 6Department of Medicine, McGill University, Montréal, Québec H3G 1Y6, Canada;
  7. 7Department of Oncology, McGill University, Montréal, Québec H3G 1Y6, Canada

    Abstract

    Estrogen-related receptor α (ERRα) and proliferator-activated 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 ERRα 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.

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    1. Published in Advance March 1, 2010, doi: 10.1101/gad.1871610 Genes & Dev. 24: 537-542 Copyright © 2010 by Cold Spring Harbor Laboratory Press

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