Identification of TRACs (T3 receptor-associating cofactors), a family of cofactors that associate with, and modulate the activity of, nuclear hormone receptors.

Nuclear hormone receptors are the largest known family of eukaryotic transcription factors and serve as critical effectors of vertebrate homeostasis, growth, and differentiation. The precise transcriptional response mediated by a given nuclear hormone receptor is dictated by hormone, promoter, and cellular context, and many nuclear hormone receptors function bimodally as both transcriptional activators and repressors. We report here the identification of a family of proteins, denoted TRACs (T3 receptor-associating cofactors), which physically interact with nuclear hormone receptors and can modulate the transcriptional properties of these receptors. TRACs associate with retinoic acid, retinoid X, and thyroid hormone receptors, as well as the PML-RAR alpha and v-Erb A oncoproteins. Certain TRAC forms attenuate target gene expression and may serve as corepressors, whereas other TRAC family members appear to counteract these effects. We suggest that TRACs and related cofactors may participate in dictating the pleiotropic transcriptional capacities of the nuclear hormone receptors.