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

doi:10.1101/gad.1871610

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 journal › Article › peer-review

111 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 language	English (US)
Pages (from-to)	537-542
Number of pages	6
Journal	Genes and Development
Volume	24
Issue number	6
DOIs	https://doi.org/10.1101/gad.1871610
State	Published - Mar 15 2010
Externally published	Yes

Keywords

ChIP-on-chip
Homeobox
Mitochondrial respiration
Nuclear receptor
Regulon

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.1871610

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

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.",

keywords = "ChIP-on-chip, Homeobox, Mitochondrial respiration, Nuclear receptor, Regulon",

author = "Alexis Charest-Marcotte and Dufour, {Catherine R.} and Wilson, {Brian J.} and Tremblay, {Annie M.} and Eichner, {Lillian J.} and Arlow, {Daniel H.} and Mootha, {Vamsi K.} and Vincent Gigu{\`e}re",

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month = mar,

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doi = "10.1101/gad.1871610",

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journal = "Genes and Development",

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AU - Charest-Marcotte, Alexis

AU - Dufour, Catherine R.

AU - Wilson, Brian J.

AU - Tremblay, Annie M.

AU - Eichner, Lillian J.

AU - Arlow, Daniel H.

AU - Mootha, Vamsi K.

AU - Giguère, Vincent

PY - 2010/3/15

Y1 - 2010/3/15

N2 - 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.

AB - 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.

KW - ChIP-on-chip

KW - Homeobox

KW - Mitochondrial respiration

KW - Nuclear receptor

KW - Regulon

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JF - Genes and Development

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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