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

被引：120
|
作者：
Charest-Marcotte, Alexis [1 ,2 ]
Dufour, Catherine R. [1 ]
Wilson, Brian J. [1 ]
Tremblay, Annie M. [1 ,2 ]
Eichner, Lillian J. [1 ,2 ]
Arlow, Daniel H. [3 ,4 ,5 ]
Mootha, Vamsi K. [3 ,4 ,5 ]
Giguere, Vincent [1 ,2 ,6 ,7 ]
机构：
[1] McGill Univ, Goodman Canc Ctr, Montreal, PQ H3A 1A3, Canada
[2] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[3] Massachusetts Gen Hosp, Dept Syst Biol, Cambridge, MA 02142 USA
[4] Massachusetts Gen Hosp, Ctr Human Genet Res, Cambridge, MA 02142 USA
[5] MIT Harvard, Broad Inst, Cambridge, MA 02142 USA
[6] McGill Univ, Dept Med, Montreal, PQ H3G 1Y6, Canada
[7] McGill Univ, Dept Oncol, Montreal, PQ H3G 1Y6, Canada
来源：
GENES & DEVELOPMENT | 2010年 / 24卷 / 06期
关键词：
ChIP-on-chip; homeobox; mitochondrial respiration; nuclear receptor; regulon; ERR-ALPHA; LIVER DEVELOPMENT; RECEPTOR-ALPHA; COUP-TFII; TRANSCRIPTION; HOMEOSTASIS; PROMOTERS; MARKER; MOTIFS;
D O I：
10.1101/gad.1871610
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Estrogen-related receptor alpha (ERR alpha) and proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) 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-1 alpha, occupies promoters of metabolic genes on a genome-wide scale, and inhibits the activity of the ERR alpha/PGC-1 alpha complex. DNA motif analysis suggests that Prox1 interacts with the genome through tethering to ERR alpha and other factors. Importantly, ablation of Prox1 and ERR alpha have opposite effects on the respiratory capacity of liver cells, revealing an unexpected role for Prox1 in the control of energy homeostasis.
引用
收藏
页码：537 / 542
页数：6
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