Modulation of Nuclear Receptor Function by Chromatin Modifying Factor TIP60

Nuclear receptors (NRs) are transcription factors that bind to specific DNA sequences known as hormone response elements located upstream of their target genes. Transcriptional activity of NRs can be modulated by binding of the compatible ligand and transient interaction with cellular coregulators, functioning either as coactivators or as corepressors. Many coactivator proteins possess intrinsic histone acetyltransferase (HAT) activity that catalyzes the acetylation of specific lysine residues in histone tails and loosens the histone-DNA interaction, thereby facilitating access of transcriptional factors to the regulatory sequences of the DNA. Tat interactive protein 60 (TIP60), a member of the Mof-Ybf2-Sas2-TIP60 family of HAT protein, is a multifunctional coregulator that controls a number of physiological processes including apoptosis, DNA damage repair, and transcriptional regulation. Over the last two decades or so, TIP60 has been extensively studied for its role as NR coregulator, controlling various aspect of steroid receptor functions. The aim of this review is to summarize the findings on the role of TIP60 as a coregulator for different classes of NRs and its overall functional implications. We also discuss the latest studies linking TIP60 to NR-associated metabolic disorders and cancers for its potential use as a therapeutic drug target in future.