| Abstract: |
Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16 is a zinc-finger protein that controls brown fat determination by stimulating brown fat-selective gene expression, while suppressing the expression of genes selective for white fat cells. To determine the mechanisms regulating this switching of gene programs, we purified native PRDM16 protein complexes from fat cells. We show here that the PRDM16 transcriptional holocompex contains C-terminal-binding protein-1 (CtBP-1) and CtBP-2, and this direct interaction selectively mediates the repression of white fat genes. This repression occurs through recruiting a PRDM16/CtBP complex onto the promoters of white fat-specific genes such as resistin, and is abolished in the genetic absence of CtBP-1 and CtBP-2. In turn, recruitment of PPAR-γ-coactivator-1α (PGC-1α) and PGC-1β to the PRDM16 complex displaces CtBP, allowing this complex to powerfully activate brown fat genes, such as PGC-1α itself. These data show that the regulated docking of the CtBP proteins on PRDM16 controls the brown and white fat-selective gene programs. © 2008 by Cold Spring Harbor Laboratory Press. |
| Keywords: |
controlled study; dna-binding proteins; nonhuman; animal cell; mouse; animals; mice; gene expression; models, biological; protein binding; genetic transcription; protein interaction; cell differentiation; transcription, genetic; cercopithecus aethiops; cos cells; transcription factors; gene expression regulation; gene repression; phosphoproteins; binding protein; gene control; multiprotein complexes; c terminal binding protein 2; 3t3 cells; adipocyte; adipogenesis; alcohol oxidoreductases; ctbp; pgc-1; ppar-γ; prdm16; resistin; c terminal binding protein 1; peroxisome proliferator activated receptor gamma coactivator 1alpha; peroxisome proliferator activated receptor gamma coactivator 1beta; 3t3-l1 cells; adipose tissue, brown; adipose tissue, white; genes, regulator
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