Zilbauer Matthias, Kraiczy Judith
Nestle Nutr Inst Workshop Ser. 2017;88:35-44. doi: 10.1159/000455211. Epub 2017 Mar 27.
Epigenetics can be defined as stable, potentially heritable changes in cellular phenotype caused by mechanisms other than alterations in the underlying DNA sequence. DNA methylation is amongst the most intensely studied epigenetic mechanisms and has been shown to play a major role in regulating fundamental aspects of cell biology including cellular differentiation, organ development, and cell type-specific gene expression. Importantly, it is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment and are able to mediate environmental changes into stable phenotypic alterations. Given existing evidence supporting the important effects of environmental factors (e.g., diet, nutrition, and infections) on human health, epigenetic mechanisms provide a plausible mechanistic framework for the development of many multifactorial diseases including inflammatory bowel disease (IBD). Impaired function of the intestinal epithelium has been implicated in IBD pathogenesis, yet underlying mechanisms remain ill defined. The work of our group focuses on investigating the role of DNA methylation in regulating cellular function of the human intestinal epithelium during gastrointestinal health and IBD. In addition to performing an analysis of primary human intestinal epithelium, we utilize human intestinal organoid culture systems allowing us to perform functional analysis in a patient-derived ex vivo model.
由潜在DNA序列改变以外的机制引起的细胞表型的稳定且可能遗传的变化。DNA甲基化是研究最为深入的表观遗传机制之一，已被证明在调节细胞生物学的基本方面发挥着重要作用，包括细胞分化、器官发育和细胞类型特异性基因表达。重要的是，越来越清楚的是，表观遗传机制在遗传密码与我们的环境之间的界面起作用，并且能够将环境变化介导为稳定的表型改变。鉴于现有证据支持环境因素（如饮食、营养和感染）对人类健康的重要影响，表观遗传机制为包括炎症性肠病（IBD）在内的许多多因素疾病的发展提供了一个合理的机制框架。肠道上皮功能受损与IBD发病机制有关，但其潜在机制仍不清楚。我们小组的工作重点是研究DNA甲基化在胃肠道健康和IBD期间调节人肠道上皮细胞功能中的作用。除了对原代人肠道上皮进行分析外，我们还利用人肠道类器官培养系统，使我们能够在患者来源的体外模型中进行功能分析。
