Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia; Faculty of Science, Engineering and Technology, Swinburne University of Technology, Hawthorn, Victoria 3122, Australia.
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, 75 Commercial Road, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.
Mol Aspects Med. 2017 Apr;54:1-15. doi: 10.1016/j.mam.2016.09.004. Epub 2016 Sep 30.
The regulation of gene expression in response to environmental and behavioural cues is critical for many biological processes. Histone tail modifications are dynamic and, as such, can regulate gene expression in response to extracellular conditions. Many of the enzymes involved in adding and removing these modifications require cofactors that are products of intermediary metabolism pathways, thus linking cellular metabolism to the regulation of gene expression. Furthermore, the expression and activity of such enzymes are influenced by the cellular concentrations of metabolic products. Under- and over-nutrition can induce epigenetic changes that influence chromatin structure and define a metabolic program. Importantly, recent studies have demonstrated that such changes during the pre- and peri-natal periods can be long-lasting, influencing the disease risk later in life and could be transmitted to subsequent generations. Moreover, damaging gene expression patterns observed in metabolic diseases such as diabetes are driven by persistent changes in chromatin structure, raising the possibility of targeting epigenetic pathways for the treatment of disease.
基因表达的调控对许多生物学过程至关重要，包括对环境和行为线索的反应。组蛋白尾部修饰是动态的，因此可以响应细胞外条件调节基因表达。许多参与添加和去除这些修饰的酶需要辅助因子，这些辅助因子是中间代谢途径的产物，从而将细胞代谢与基因表达的调控联系起来。此外，这些酶的表达和活性受到代谢产物的细胞浓度的影响。营养不良和营养过剩会诱导影响染色质结构和定义代谢程序的表观遗传变化。重要的是，最近的研究表明，在产前和围产期发生的这些变化可能是持久的，会影响以后生活中的疾病风险，并可能传递给后代。此外，在糖尿病等代谢疾病中观察到的破坏基因表达模式是由染色质结构的持续变化驱动的，这增加了针对表观遗传途径治疗疾病的可能性。
