Dressler Gregory R, Patel Sanjeevkumar R
Department of Pathology, University of Michigan, Ann Arbor, Mich.
Department of Internal Medicine, University of Michigan, Ann Arbor, Mich.
Transl Res. 2015 Jan;165(1):166-76. doi: 10.1016/j.trsl.2014.04.007. Epub 2014 Jun 4.
The study of epigenetics is intimately linked and inseparable from developmental biology. Many of the genes that imprint epigenetic information on chromatin function during the specification of cell lineages in the developing embryo. These include the histone methyltransferases and their cofactors of the Polycomb and Trithorax gene families. How histone methylation is established and what regulates the tissue and locus specificity of histone methylation is an emerging area of research. The embryonic kidney is used as a model to understand how DNA-binding proteins can specify cell lineages and how such proteins interact directly with the histone methylation machinery to generate a unique epigenome for particular tissues and cell types. In adult tissues, histone methylation marks must be maintained for normal gene expression patterns. In chronic and acute renal disease, epigenetic marks are being characterized and correlated with the establishment of metabolic memory, in part to explain the persistence of pathologies even when optimal treatment modalities are used. Thus, the state of the epigenome in adult cells must be considered when attempting to alleviate or alter gene expression patterns in disease.
表观遗传学的研究与发育生物学紧密相连、不可分割。在发育胚胎的细胞谱系特化过程中,许多基因会在染色质功能上印记表观遗传信息。这些基因包括多梳蛋白和三胸节基因家族的组蛋白甲基转移酶及其辅助因子。组蛋白甲基化是如何建立的,以及是什么调节组蛋白甲基化的组织和位点特异性,是一个新兴的研究领域。胚胎肾被用作模型,以了解DNA结合蛋白如何指定细胞谱系,以及这些蛋白如何直接与组蛋白甲基化机制相互作用,从而为特定组织和细胞类型生成独特的表观基因组。在成体组织中,必须维持组蛋白甲基化标记以保持正常的基因表达模式。在慢性和急性肾病中,表观遗传标记正在被表征,并与代谢记忆的建立相关联,部分原因是为了解释即使使用最佳治疗方式,病理状态仍会持续存在的现象。因此,在试图缓解或改变疾病中的基因表达模式时,必须考虑成体细胞中表观基因组的状态。