The role of genetic mutations in the development of polycystic kidney disease (PKD), such as alterations in PKD1 and PKD2 genes in autosomal dominant PKD (ADPKD), is well understood. However, the significance of epigenetic mechanisms in the progression of PKD remains unclear and is increasingly being investigated. The term of epigenetics describes a range of mechanisms in genome function that do not solely result from the DNA sequence itself. Epigenetic information can be inherited during mammalian cell division to sustain phenotype specifically and physiologically responsive gene expression in the progeny cells. A multitude of functional studies of epigenetic modifiers and systematic genome-wide mapping of epigenetic marks reveal the importance of epigenomic mechanisms, including DNA methylation, histone/chromatin modifications and non-coding RNAs, in PKD pathologies. Deregulated proliferation is a characteristic feature of cystic renal epithelial cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cyst formation and progression. Recent evidence suggests that alterations of DNA methylation and histone modifications on specific genes and the whole genome involved in cell cycle regulation and contribute to the pathogenesis of PKD. This review summarizes the recent advances of epigenetic mechanisms in PKD, which helps us to define the term of "PKD epigenetics" and group PKD epigenetic changes in three categories. In particularly, this review focuses on the interplay of epigenetic mechanisms with cell cycle regulation during normal cell cycle progression and cystic cell proliferation, and discusses the potential to detect and quantify DNA methylation from body fluids as diagnostic/prognostic biomarkers. Collectively, this review provides concepts and examples of epigenetics in cell cycle regulation to reveal a broad view of different aspects of epigenetics in biology and PKD, which may facilitate to identify possible novel therapeutic intervention points and to explore epigenetic biomarkers in PKD.

中文翻译：

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囊胚发生中的表观遗传学和细胞周期调控。

遗传突变在多囊性肾病（PKD）的发生中的作用，例如常染色体显性PKD（ADPKD）中PKD1和PKD2基因的改变，是众所周知的。然而，表观遗传机制在PKD进程中的重要性尚不清楚，并且正在被越来越多的研究。表观遗传学一词描述了基因组功能中的一系列机制，这些机制不仅仅来自DNA序列本身。可以在哺乳动物细胞分裂过程中继承表观遗传信息，以在子代细胞中维持特定的表型和生理应答基因表达。对表观遗传修饰符的大量功能研究以及对表观遗传标记的系统性全基因组作图揭示了表观基因组机制的重要性，包括DNA甲基化，PKD病理中的组蛋白/染色质修饰和非编码RNA。增殖失调是肾囊性上皮细胞的特征。而且，调节细胞周期的许多分子中的缺陷与囊肿的形成和发展有关。最近的证据表明，DNA甲基化的改变以及特定基因和整个基因组上涉及细胞周期调控的组蛋白修饰均与PKD的发病机理有关。这篇综述总结了PKD表观遗传机制的最新进展，这有助于我们定义“ PKD表观遗传学”一词，并将PKD表观遗传学分为三类。特别是，这篇综述着重于表观遗传机制与正常细胞周期进程和囊性细胞增殖过程中细胞周期调控之间的相互作用，并讨论了检测和定量化体液中DNA甲基化作为诊断/预后生物标志物的潜力。总的来说，本综述提供了细胞周期调控中表观遗传学的概念和实例，以揭示生物学和PKD中表观遗传学不同方面的广泛观点，这可能有助于鉴定可能的新型治疗干预点并探索PKD中的表观遗传生物标志物。