Non-steroid nuclear receptors include thyroid hormone receptor, retinoic acid receptor, vitamin D receptor, Liver X receptor like receptors (LXR and FXR) and PPARγ. Members of this family heterodimerize with the retinoid X receptor (RXR). Prior to ligand binding, receptor heterodimers are located in the nucleus as part of complexes with histone deacetylases (HDACs) and other corepressors that keep target DNA in a tightly wound conformation, preventing exposure to transactivation factors. Ligand binding results in HDAC dissociation, chromatin derepression, and transcriptional activation.In addition to ligand binding, nuclear receptor activity can be modulated through the action of numerous growth factor and cytokine signaling cascades that result in receptor phosphorylation or other post-translational modifications, typically within the N-terminal transactivation domain. .