Transcription factors exert their effects by associating with co-activator or corepressor proteins. The co-activator complexes are thought to be constitutively active, requiring only proper positioning in the genome to initiate transcription. Co-activators include the steroid receptor coactivator (SRC) and CREB binding protein (CBP) families that contain histone acetyltransferase (HAT) activity, which modifies chromatin structure. PPARgamma co-activator-1 (PGC-1) is a transcriptional cofactor of nuclear respiratory factor-1 (NRF-1), PPARbeta, PPARalpha and other nuclear receptors that is induced by exposure to cold temperatures and is involved in regulating thermogenic gene expression, protein uncoupling, and mitochondrial biogenesis. PGC-1 has a low inherent transcriptional activity when it is not bound to a transcription factor. Docking of PGC-1 to PPARgamma stimulates an apparent conformational change that then enables PGC-1 to bind to and assemble into complexes, which include the additional cofactors SRC-1 and CBP/p300, and results in a large increase in transcriptional activity.
