Jorgensen Brian G, Ro Seungil
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, USA.
J Neurogastroenterol Motil. 2019 Jul 1;25(3):377-386. doi: 10.5056/jnm19077.
The mammalian intestine contains many different cell types but is comprised of 2 main cell types: epithelial cells and smooth muscle cells. Recent in vivo and in vitro evidence has revealed that various alterations to the DNA methylation apparatus within both of these cell types can result in a variety of cellular phenotypes including modified differentiation status, apoptosis, and uncontrolled growth. Methyl groups added to cytosines in regulatory genomic regions typically act to repress associated gene transcription. Aberrant DNA methylation patterns are often found in cells with abnormal growth/differentiation patterns, including those cells involved in burdensome intestinal pathologies including inflammatory bowel diseases and intestinal pseudo-obstructions. The altered methylation patterns being observed in various cell cultures and DNA methyltransferase knockout models indicate an influential connection between DNA methylation and gastrointestinal cells' development and their response to environmental signaling. As these modified DNA methylation levels are found in a number of pathological gastrointestinal conditions, further investigations into uncovering the causative nature, and controlled regulation, of this epigenetic modification is of great interest.
哺乳动物的肠道包含许多不同的细胞类型,但主要由两种细胞类型组成:上皮细胞和平滑肌细胞。最近的体内和体外证据表明,这两种细胞类型内DNA甲基化机制的各种改变可导致多种细胞表型,包括改变的分化状态、凋亡和不受控制的生长。添加到调控基因组区域胞嘧啶上的甲基通常起到抑制相关基因转录的作用。异常的DNA甲基化模式经常出现在具有异常生长/分化模式的细胞中,包括那些参与严重肠道疾病(如炎症性肠病和肠道假性梗阻)的细胞。在各种细胞培养和DNA甲基转移酶基因敲除模型中观察到的甲基化模式改变表明,DNA甲基化与胃肠道细胞发育及其对环境信号的反应之间存在重要联系。由于在许多病理性胃肠道疾病中都发现了这些改变的DNA甲基化水平,因此进一步研究这种表观遗传修饰的致病本质及其可控调节具有重要意义。