Nuclear Receptors in Nonalcoholic Fatty Liver Disease
(a) Schematic representation of a typical nuclear receptor. Nuclear receptors may be divided into five regions based on structural and functional similarities (denoted A, B, C, D, E, and F). Regions C and E contain the conserved DNA-binding domains (DBDs) and ligand-binding domains (LBDs) that are the signature of this superfamily. In addition, the constitutive transport element (CTE) is a dimerization region within the LBD and two transactivation domains (denoted AF-1 and AF-2/τc). A second dimerization domain (not shown) exists in the DBD and is required for heterodimerization of receptors on response elements. (b) NR function. Ligand binding to NRs triggers changes in their conformation leading to the dissociation of corepressors and the recruitment of coactivators. After this exchange of coregulators, RNA polymerase II is recruited and mRNA transcription is initiated. Most NRs bind to their DNA response elements in a sequence-specific manner as dimers, functioning either as homodimers or as heterodimers with the RXR. RA: retinoic acid. Modified from [13, 94].