Ménage-à-Trois 1 Is Critical for the Transcriptional Function of PPARγ Coactivator 1

Academic Article


  • The Cdk7/cyclin H/ménage-à-trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by Gq-, calcineurin-, and biomechanical stress-dependent pathways for hypertrophic growth. Using cardiac-specific Cre, we have ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally, but fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1α failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1α was functionally defective, and PGC-1β was likewise deficient. PGC-1 bound to both MAT1 and Cdk7 in coprecipitation assays. Thus, we demonstrate a requirement for MAT1 in the operation of PGC-1 coactivators that control cell metabolism. © 2007 Elsevier Inc. All rights reserved.
  • Authors

    Published In

  • Cell Metabolism  Journal
  • Digital Object Identifier (doi)

    Author List

  • Sano M; Izumi Y; Helenius K; Asakura M; Rossi DJ; Xie M; Taffet G; Hu L; Pautler RG; Wilson CR
  • Start Page

  • 129
  • End Page

  • 142
  • Volume

  • 5
  • Issue

  • 2