chapter  7
12 Pages

Nutrigenomic Implications for Nuclear Receptor Coactivators

As transcription factors, NRs have a direct role in regulating the expression of hormone-response genes. This regulatory capacity of NRs occurs through their ability to recognize specic sequences in the promoters of their target genes, and their relationships with the RNA polymerase II holocomplex and the chromatin environment that surrounds these genes (Tsai and O’Malley 1994). Central to our discussion here, coactivators have broad genome-wide effects on gene expression through their ability to interact with numerous NRs and other non-NR transcription factors. Coactivators also have counterparts known as corepressors that act in an opposite manner to repress gene expression, primarily through their interaction with unliganded NRs (Torchia et al. 1998). Here, we will focus on the coactivators, as they have been more broadly studied, particularly with regard to the regulation of energy

Introduction .................................................................................................................................... 161 Molecular Aspects of Coactivators ................................................................................................ 162 Coactivators Function as Multiprotein Complexes ........................................................................ 162

Coactivators Are Master Regulators of Gene Expression Programs ......................................... 162 SRC Family Members Are Key Oncogenic Coactivators ......................................................... 164

Coactivator Bioinformatics ............................................................................................................ 165 Coregulator Involvement in Energy Metabolism ...................................................................... 166 Coactivators, Diet, and Human Evolution ................................................................................. 166 Coactivators as Low Penetrance Disease Risk Alleles .............................................................. 167

Concluding Remarks ...................................................................................................................... 168 References ...................................................................................................................................... 169

metabolism. Depending upon cell and signaling contexts, coactivators and corepressors can sometimes switch roles. Presently, more than 350 coregulators have been reported in the literature, frequently in connection with numerous physiological functions and pathological states (Lonard et al. 2007).