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DNA甲基化羟化酶TET1的研究进展

Advances in the DNA methylation hydroxylase TET1.

作者信息

Liu Wenzheng, Wu Guanhua, Xiong Fei, Chen Yongjun

机构信息

Department of Biliary and Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.

出版信息

Biomark Res. 2021 Oct 16;9(1):76. doi: 10.1186/s40364-021-00331-7.

Abstract

BACKGROUND

The ten-eleven translocation 1 (TET1) protein is a 5-methylcytosine hydroxylase that belongs to the TET protein family of human α-ketoglutarate oxygenases. TET1 recognizes and binds to regions of high genomic 5'-CpG-3' dinucleotide density, such as CpG islands, initiates the DNA demethylation program, and maintains DNA methylation and demethylation balance to maintain genomic methylation homeostasis and achieve epigenetic regulation. This article reviews the recent research progress of TET1 in the mechanism of demethylation, stem cells and immunity, various malignant tumours and other clinical diseases.

CONCLUSION

TET1 acts as a key factor mediating demethylation, the mechanism of which still remains to be investigated in detail. TET1 is also critical in maintaining the differentiation pluripotency of embryonic stem cells and plays anti- or oncogenic roles in combination with different signalling pathways in different tumours. In certain tumours, its role is still controversial. In addition, the noncatalytic activity of TET1 has gradually attracted attention and has become a new direction of research in recent years.

摘要

背景

10-11易位蛋白1(TET1)是一种5-甲基胞嘧啶羟化酶,属于人类α-酮戊二酸加氧酶的TET蛋白家族。TET1识别并结合高基因组5'-CpG-3'二核苷酸密度区域,如CpG岛,启动DNA去甲基化程序,并维持DNA甲基化和去甲基化平衡,以维持基因组甲基化稳态并实现表观遗传调控。本文综述了TET1在去甲基化机制、干细胞与免疫、各种恶性肿瘤及其他临床疾病方面的最新研究进展。

结论

TET1作为介导去甲基化的关键因子,其机制仍有待深入研究。TET1在维持胚胎干细胞分化多能性方面也至关重要,并在不同肿瘤中与不同信号通路结合发挥抑癌或致癌作用。在某些肿瘤中,其作用仍存在争议。此外,TET1的非催化活性逐渐受到关注,已成为近年来新的研究方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8520278/38328895d97b/40364_2021_331_Fig1_HTML.jpg

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