Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK.
J Neuroendocrinol. 2011 Jan;23(1):94-106. doi: 10.1111/j.1365-2826.2010.02079.x.
Epigenetic mechanisms alter the structure of local chromosome domains to dynamically regulate gene expression by signalling and propagating transcriptional states. Nuclear receptors, a stimulus-inducible class of transcription factors, interact with chromatin to regulate transcription. To promote transcription, nuclear receptors interact with genomic regulatory elements that are epigenetically marked by modified histone tails, DNA methylation status, histone variants, chromatin accessibility and long-range interactions. Advances in throughput have allowed the profiling of regulatory factor activity on a genome-wide scale, with recent evidence from genomic analyses highlighting novel aspects of DNA-binding factor actions on chromatin. In the present review, the current knowledge of the mechanisms regulating nuclear receptor occupancy at cis-regulatory elements is discussed, with particular emphasis on the glucocorticoid, oestrogen and androgen receptors. Epigenetic regulation of genomic elements direct cell-specific regulatory factor binding and contribute to human variation in factor occupancy. Through regulating nuclear receptor activity, the epigenome is a critical checkpoint in nuclear receptor induced gene expression in health and disease.
表观遗传机制改变局部染色体结构域的结构，通过信号转导和转录状态的传播来动态调节基因表达。核受体是一类受刺激诱导的转录因子，与染色质相互作用以调节转录。为了促进转录，核受体与基因组调控元件相互作用，这些元件通过修饰的组蛋白尾部、DNA 甲基化状态、组蛋白变体、染色质可及性和长程相互作用来进行表观遗传标记。高通量技术的进步使得能够在全基因组范围内对调控因子活性进行分析，最近的基因组分析证据强调了 DNA 结合因子在染色质上的作用的新方面。在本综述中，讨论了调节顺式调控元件上核受体占据的机制的现有知识，特别强调了糖皮质激素受体、雌激素受体和雄激素受体。基因组元件的表观遗传调控指导细胞特异性调控因子结合，并导致人类在因子占据方面的变异。通过调节核受体活性，表观基因组是核受体诱导的健康和疾病中基因表达的关键检查点。
