了解十-十一转位家族蛋白在肾脏疾病中的作用。

IF 3.8 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Society transactions Pub Date : 2024-10-30 DOI:10.1042/BST20240291
Yuelin Zhang, Jiahui Li, Li Tan, Jun Xue, Yujiang Geno Shi
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引用次数: 0

摘要

表观遗传机制在包括肾脏疾病在内的人类疾病的发病机制中起着至关重要的作用。作为 DNA 甲基化的侵蚀者,十-十一转位(TET)家族蛋白可将 5-甲基胞嘧啶(5mC)氧化为 5-羟甲基胞嘧啶(5hmC)、5-甲酰基胞嘧啶(5fC)和 5-羧基胞嘧啶(5caC),从而导致被动或主动的 DNA 去甲基化。同样,TET 家族蛋白也能催化 RNA 上的相同反应。此外,TET家族蛋白还能通过招募SIN3A/HDAC共抑制因子复合物,以一种与催化活性无关的方式调控染色质结构和基因表达。2012 年,我们首次报道了小鼠肾脏缺血再灌注损伤后,基因组中 5-羟甲基胞嘧啶水平以及 Tet1 和 Tet2 的 mRNA 水平显著下调。此后,越来越多的证据最终证实,TET 家族蛋白不仅在急性肾损伤中发挥着不可或缺的作用,而且在慢性肾脏疾病中也发挥着重要作用。在这篇综述中,我们总结了 TET 家族蛋白在主要类型肾脏疾病中的上游调控机制和病理生理作用,并讨论了它们在临床诊断和治疗中的潜在价值。
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Understanding the role of ten-eleven translocation family proteins in kidney diseases.

Epigenetic mechanisms play a critical role in the pathogenesis of human diseases including kidney disorders. As the erasers of DNA methylation, Ten-eleven translocation (TET) family proteins can oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), thus leading to passive or active DNA demethylation. Similarly, TET family proteins can also catalyze the same reaction on RNA. In addition, TET family proteins can also regulate chromatin structure and gene expression in a catalytic activity-independent manner through recruiting the SIN3A/HDAC co-repressor complex. In 2012, we reported for the first time that the genomic 5-hydroxymethylcytosine level and the mRNA levels of Tet1 and Tet2 were significantly downregulated in murine kidneys upon ischemia and reperfusion injury. Since then, accumulating evidences have eventually established an indispensable role of TET family proteins in not only acute kidney injury but also chronic kidney disease. In this review, we summarize the upstream regulatory mechanisms and the pathophysiological role of TET family proteins in major types of kidney diseases and discuss their potential values in clinical diagnosis and treatment.

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来源期刊
Biochemical Society transactions
Biochemical Society transactions 生物-生化与分子生物学
CiteScore
7.80
自引率
0.00%
发文量
351
审稿时长
3-6 weeks
期刊介绍: Biochemical Society Transactions is the reviews journal of the Biochemical Society. Publishing concise reviews written by experts in the field, providing a timely snapshot of the latest developments across all areas of the molecular and cellular biosciences. Elevating our authors’ ideas and expertise, each review includes a perspectives section where authors offer comment on the latest advances, a glimpse of future challenges and highlighting the importance of associated research areas in far broader contexts.
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