Department of Internal Medicine, Department of Internal Medicine (463), Radboud University Medical Center, Nijmegen, PO Box 9101, 6500 HB, Nijmegen, the Netherlands.
Central Clinical School, Monash University, 99 Commercial Road, Melbourne, VIC, 3004, Australia.
Diabetologia. 2018 Jan;61(1):6-20. doi: 10.1007/s00125-017-4490-1. Epub 2017 Nov 11.
When it comes to the epigenome, there is a fine line between clarity and confusion-walk that line and you will discover another fascinating level of transcription control. With the genetic code representing the cornerstone of rules for information that is encoded to proteins somewhere above the genome level there is a set of rules by which chemical information is also read. These epigenetic modifications show a different side of the genetic code that is diverse and regulated, hence modifying genetic transcription transiently, ranging from short- to long-term alterations. While this complexity brings exquisite control it also poses a formidable challenge to efforts to decode mechanisms underlying complex disease. Recent technological and computational advances have improved unbiased acquisition of epigenomic patterns to improve our understanding of the complex chromatin landscape. Key to resolving distinct chromatin signatures of diabetic complications is the identification of the true physiological targets of regulatory proteins, such as reader proteins that recognise, writer proteins that deposit and eraser proteins that remove specific chemical moieties. But how might a diverse group of proteins regulate the diabetic landscape from an epigenomic perspective? Drawing from an ever-expanding compendium of experimental and clinical studies, this review details the current state-of-play and provides a perspective of chromatin-dependent mechanisms implicated in diabetic complications, with a special focus on diabetic nephropathy. We hypothesise a codified signature of the diabetic epigenome and provide examples of prime candidates for chemical modification. As for the pharmacological control of epigenetic marks, we explore future strategies to expedite and refine the search for clinically relevant discoveries. We also consider the challenges associated with therapeutic strategies targeting epigenetic pathways.
当涉及到表观基因组时，在清晰度和混淆之间存在着细微的界限——沿着这条线走，你将发现转录控制的另一个迷人层次。遗传密码代表了位于基因组水平之上的蛋白质编码信息规则的基石，还有一套规则可以读取化学信息。这些表观遗传修饰展示了遗传密码的不同方面，它是多样且受调控的，因此可以暂时改变基因转录，从短期到长期的改变。虽然这种复杂性带来了精细的控制，但它也给解码复杂疾病背后的机制带来了巨大的挑战。最近的技术和计算进展提高了对表观基因组模式的无偏获取，从而提高了我们对复杂染色质景观的理解。解决糖尿病并发症独特染色质特征的关键是确定调节蛋白（如识别特定化学基团的阅读器蛋白、沉积特定化学基团的写入器蛋白和去除特定化学基团的擦除器蛋白）的真正生理靶标。但是，从表观基因组的角度来看，一组多样化的蛋白质如何调节糖尿病的发生呢？本文从不断扩展的实验和临床研究汇编中汲取灵感，详细描述了目前的研究现状，并提供了与糖尿病并发症相关的染色质依赖性机制的观点，特别关注糖尿病肾病。我们假设了糖尿病表观基因组的编码特征，并提供了化学修饰的主要候选者的例子。至于表观遗传标记的药理学控制，我们探讨了加速和完善寻找临床相关发现的未来策略。我们还考虑了针对表观遗传途径的治疗策略所带来的挑战。
