PGC-1 and PERC, coactivators of the estrogen receptor-related receptor gamma.
The mouse nuclear receptor ERRgamma (estrogen receptor-related receptor gamma) is highly expressed in heart, skeletal muscle, kidney, and brain, as well as in the developing nervous system. We found that the expression of the coactivators PGC-1 (PGC-1alpha) and PERC (PGC-1beta) in mammalian cells augmented potently the transcriptional activation by ERRgamma. The constitutive activation function 2 (AF-2) of the orphan receptor was important for the synergistic enhancement. Functional receptor truncation analysis revealed an additional amino-terminal activation function, specific for the ERRgamma2 isoform and PGC-1. In vitro experiments showed a direct interaction of ERRgamma with both coactivators. Our findings suggest distinct regulatory functions for PGC-1 and PERC as tissue-specific coactivators for ERRgamma.
Hentschke
Moritz
M
Zentrum für Molekulare Neurobiologie, Institut für Entwicklungsneurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany.
Süsens
Ute
U
Borgmeyer
Uwe
U
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D051379:Mice; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D011960:Receptors, Estrogen; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D002352:Carrier Proteins; C490917:ESRRG protein, human; C098925:Esrrb protein, mouse; C490916:Esrrg protein, mouse; C455622:PPARGC1B protein, human; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1