Abstract
An important aspect of molecular toxicology is the ability of a wide array of xenobiotics to alter gene transcription through soluble receptors. Over the past 20years mechanistic studies have examined the ability of these receptors to be activated by ligands and subsequently bind to enhancer elements upstream of a promoter for a given gene. In this chapter coregulators are defined as proteins or protein complexes that are recruited either directly or indirectly to nuclear receptors (NRs) and either enhance or repress transactivation potential. Recent evidence suggests that enzymatic activities associated with coregulator complexes are required for modifying specific components of the primary transcriptional machinery and chromatin structure in a cell-, gene-, and promoter-specific manner. Coregulators can thus be broadly grouped as coactivators, which enhance, and corepressors that inhibit, gene transcription. In general, transcriptional activation involves several processes including: activation of enhancer binding factors, competition for overlapping enhancer sites, release of corepressors, and subsequent recruitment of coactivators. Coregulators are versatile proteins that influence a number of processes associated with gene expression, including: transcription initiation, elongation, mRNA splicing, and translation. Furthermore, coactivators are key regulators of nuclear receptors that modulate receptor activity key to human health and disease (Dasgupta et al., 2014).
Original language | English (US) |
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Title of host publication | Comprehensive Toxicology, Third Edition |
Subtitle of host publication | Volume 1-15 |
Publisher | Elsevier |
Pages | V8-55-V8-75 |
Volume | 8 |
ISBN (Electronic) | 9780081006122 |
ISBN (Print) | 9780081006016 |
DOIs | |
State | Published - Jan 1 2018 |
All Science Journal Classification (ASJC) codes
- General Agricultural and Biological Sciences
- General Environmental Science