Ferrari Alessandra, Fiorino Erika, Giudici Marco, Gilardi Federica, Galmozzi Andrea, Mitro Nico, Cermenati Gaia, Godio Cristina, Caruso Donatella, De Fabiani Emma, Crestani Maurizio
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italia.
Mol Membr Biol. 2012 Nov;29(7):257-66. doi: 10.3109/09687688.2012.729094. Epub 2012 Oct 24.
A number of recent studies revealed that epigenetic modifications play a central role in the regulation of lipid and of other metabolic pathways such as cholesterol homeostasis, bile acid synthesis, glucose and energy metabolism. Epigenetics refers to aspects of genome functions regulated in a DNA sequence-independent fashion. Chromatin structure is controlled by epigenetic mechanisms through DNA methylation and histone modifications. The main modifications are histone acetylation and deacetylation on specific lysine residues operated by two different classes of enzymes: Histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. The interaction between these enzymes and histones can activate or repress gene transcription: Histone acetylation opens and activates chromatin, while deacetylation of histones and DNA methylation compact chromatin making it transcriptionally silent. The new evidences on the importance of HDACs in the regulation of lipid and other metabolic pathways will open new perspectives in the comprehension of the pathophysiology of metabolic disorders.
近期的多项研究表明,表观遗传修饰在脂质及其他代谢途径(如胆固醇稳态、胆汁酸合成、葡萄糖和能量代谢)的调控中发挥着核心作用。表观遗传学是指以不依赖于DNA序列的方式调控基因组功能的各个方面。染色质结构通过DNA甲基化和组蛋白修饰等表观遗传机制进行控制。主要的修饰是由两类不同的酶分别作用于特定赖氨酸残基上的组蛋白乙酰化和去乙酰化:即组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)。这些酶与组蛋白之间的相互作用能够激活或抑制基因转录:组蛋白乙酰化会使染色质开放并激活,而组蛋白去乙酰化和DNA甲基化则会使染色质致密,从而使其转录沉默。关于HDACs在脂质及其他代谢途径调控中重要性的新证据,将为理解代谢紊乱的病理生理学开辟新的视角。