Huang Can-Ze, Yu Tao, Chen Qi-Kui
Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou, Guangdong, People's Republic of China .
Stem Cells Dev. 2015 Dec 1;24(23):2733-9. doi: 10.1089/scd.2015.0235. Epub 2015 Oct 20.
DNA methylation, an epigenetic control mechanism in mammals, is widely present in the intestinal tract during the differentiation and proliferation of epithelial cells. Cells in stem cell pools or villi have different patterns of DNA methylation. The process of DNA methylation is dynamic and occurs at many relevant regulatory elements during the rapid transition of stem cells into fully mature, differentiated epithelial cells. Changes in DNA methylation patterns most often take place in enhancer and promoter regions and are associated with transcription factor binding. During differentiation, enhancer regions associated with genes important to enterocyte differentiation are demethylated, activating gene expression. Abnormal patterns of DNA methylation during differentiation and proliferation in the intestinal tract can lead to the formation of aberrant crypt foci and destroy the barrier and absorptive functions of the intestinal epithelium. Accumulation of these epigenetic changes may even result in tumorigenesis. In the current review, we discuss recent findings on the association between DNA methylation and cell differentiation and proliferation in the small intestine and highlight the possible links between dysregulation of this process and tumorigenesis.
DNA甲基化是哺乳动物中的一种表观遗传控制机制，在上皮细胞分化和增殖过程中广泛存在于肠道中。干细胞池或绒毛中的细胞具有不同的DNA甲基化模式。DNA甲基化过程是动态的，在干细胞快速转变为完全成熟、分化的上皮细胞的过程中，许多相关调控元件都会发生DNA甲基化。DNA甲基化模式的变化最常发生在增强子和启动子区域，并与转录因子结合相关。在分化过程中，与肠上皮细胞分化重要基因相关的增强子区域去甲基化，激活基因表达。肠道分化和增殖过程中异常的DNA甲基化模式可导致异常隐窝灶的形成，并破坏肠上皮的屏障和吸收功能。这些表观遗传变化的积累甚至可能导致肿瘤发生。在本综述中，我们讨论了DNA甲基化与小肠细胞分化和增殖之间关联的最新研究发现，并强调了该过程失调与肿瘤发生之间的可能联系。
