Li Linda Xiaoyan, Agborbesong Ewud, Zhang Lu, Li Xiaogang
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States.
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, United States.
Methods Cell Biol. 2019;153:255-278. doi: 10.1016/bs.mcb.2019.04.015. Epub 2019 Jun 13.
Epigenetics is the study of heritable changes in DNA or its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in the processes of kidney cell biology through the action of DNA methylation, chromatin modifications via epigenetic regulators and interaction via transcription factors, and noncoding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, nephritic and nephrotic syndromes, pyelonephritis and polycystic kidney diseases are driven by aberrant activity in numerous signaling pathways in even individual kidney cell. Epigenetic alterations, including DNA methylation, histone acetylation and methylation, noncoding RNAs, and protein posttranslational modifications, could disrupt essential pathways that protect the renal cells from uncontrolled growth, apoptosis and establishment of other renal associated syndromes, which have been recognized as one of the critical mechanisms for regulating functional changes that drive and maintain the kidney disease phenotype. In this chapter, we briefly summarize the epigenetic mechanisms in kidney cell biology and epigenetic basis of kidney development, and introduce epigenetic techniques that can be used in investigating the molecular mechanism of kidney cell biology and kidneys diseases, primarily focusing on the integration of DNA methylation and chromatin immunoprecipitation technologies into kidney disease associated studies. Future studies using these emerging technologies will elucidate how alterations in the renal cell epigenome cooperate with genetic aberrations for kidney disease initiation and progression. Incorporating epigenomic testing into the clinical research is essential to future studies with epigenetics biomarkers and precision medicine using emerging epigenetic therapies.
表观遗传学是研究DNA或其相关蛋白质的可遗传变化，但不包括基因序列中的突变。表观遗传调控通过DNA甲基化、经由表观遗传调节因子的染色质修饰以及经由转录因子的相互作用，以及非编码RNA种类，在肾细胞生物学过程中发挥着基本作用。肾脏疾病，包括急性肾损伤、慢性肾病、肾炎和肾病综合征、肾盂肾炎和多囊肾病，即使在单个肾细胞中，也由众多信号通路中的异常活动所驱动。表观遗传改变，包括DNA甲基化、组蛋白乙酰化和甲基化、非编码RNA以及蛋白质翻译后修饰，可能会破坏保护肾细胞免受不受控制的生长、凋亡以及其他肾脏相关综合征发生的关键通路，这些通路已被认为是调节驱动和维持肾病表型的功能变化的关键机制之一。在本章中，我们简要总结了肾细胞生物学中的表观遗传机制以及肾脏发育的表观遗传基础，并介绍了可用于研究肾细胞生物学和肾脏疾病分子机制的表观遗传技术，主要侧重于将DNA甲基化和染色质免疫沉淀技术整合到肾脏疾病相关研究中。使用这些新兴技术的未来研究将阐明肾细胞表观基因组的改变如何与基因畸变协同作用，引发和推动肾脏疾病的发生发展。将表观基因组检测纳入临床研究对于未来使用表观遗传生物标志物和新兴表观遗传疗法的精准医学研究至关重要。
