Epigenetic regulation of the intestinal epithelium.
Epigenetic regulation of the intestinal epithelium.
复制标题
肠上皮的表观遗传调节。
DOI：
10.1007/s00018-015-1997-9
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Kaestner KH
中科院分区：
文献类型：
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作者：
Elliott EN;Kaestner KH
肠上皮是研究正常和病理分化过程的理想模型系统。哺乳动物肠上皮是由增殖的隐窝和分化的绒毛组成的单细胞层。隐窝包含增殖和静止的干细胞群体，这些干细胞群体自我更新并产生所有分化的细胞类型，每3至5天更换一次。肠道发育、内环境稳定和疾病的遗传学已得到很好的定义，但对表观遗传学在调节这些过程中的作用知之甚少。表观遗传学是指可遗传的表型性状，包括基因表达，这是独立的DNA序列中的突变。几十年来，我们已经知道人类结直肠癌含有低甲基化DNA，但这种现象的原因和后果尚未完全了解。相反，肿瘤抑制基因启动子在结直肠癌中常常是高甲基化的，导致相关基因的表达降低。在这篇综述中，我们描述了表观遗传学在肠道内稳态和疾病中的作用，重点是小鼠模型的结果。我们强调了产生和分析下一代测序数据的重要性，这些数据详细描述了从肠干细胞到分化的肠绒毛细胞的表观基因组。
The intestinal epithelium is an ideal model system for the study of normal and pathological differentiation processes. The mammalian intestinal epithelium is a single cell layer comprised of proliferative crypts and differentiated villi. The crypts contain both proliferating and quiescent stem cell populations that self-renew and produce all the differentiated cell types, which are replaced every 3 to 5 days. The genetics of intestinal development, homeostasis, and disease are well defined, but less is known about the contribution of epigenetics in modulating these processes. Epigenetics refers to heritable phenotypic traits, including gene expression, which are independent of mutations in the DNA sequence. We have known for several decades that human colorectal cancers contain hypomethylated DNA, but the causes and consequences of this phenomenon are not fully understood. In contrast, tumor suppressor gene promoters are often hypermethylated in colorectal cancer, resulting in decreased expression of the associated gene. In this review, we describe the role that epigenetics plays in intestinal homeostasis and disease, with an emphasis on results from mouse models. We highlight the importance of producing and analyzing next-generation sequencing data detailing the epigenome from intestinal stem cell to differentiated intestinal villus cell.