NuclearReceptors2018 Nuclear Receptors: New Roles for Nuclear Receptors in Development, Health and Disease Conference 2018 Plenary Lectures (3 abstracts)
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
The early work on the existence and function of the estrogen receptor (ER) primed the nuclear receptor field for an eventual explosive development. Subsequent cloning of receptors led to a realization of a giant (48) super-family of related transcription factors. The cloning of coregulators further enhanced this field in terms of mechanism of action. Nuclear receptors control gene expression by recruiting transcriptional coactivators (or corepressors) to target enhancers/promoters. These coregulator pre-initiation complexes can be modulated by histone epigenomic marks. Poised initiation complexes at enhancers then are converted to active complexes by enzymatic posttranslational modifications of the coactivator complex. Recruited coactivators read and write histone marks in the enhancer/promoter locale, and understanding the roles of these reader/writer coactivators permits new understanding of transcriptional mechanisms that can be directed toward novel approaches for disease therapies. The NR-coactivator complexes are master regulator complexes that coordinate the activation of multiple genes and pathways to control physiologies such as reproduction, growth and metabolism. Molecular mechanism studies in diverse tissues have led to the development of new drugs that bind NRs and prevent NR-mediated diseases; studies of coactivators have implicated them in many cancers (e.g., breast and prostate), in metabolic diseases of carbohydrate, lipid, anabolic and energy metabolism and in endometriosis/fertility consequently, we now can devise new approaches for treatment of many of these pathologies.
DOI: 10.1530/endoabs.54.PL2