Asset Details
Do you wish to reserve the book?
TET-mediated active DNA demethylation: mechanism, function and beyond
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
TET-mediated active DNA demethylation: mechanism, function and beyond
Do you wish to request the book?
TET-mediated active DNA demethylation: mechanism, function and beyond
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
TET-mediated active DNA demethylation: mechanism, function and beyond
2017
Overview
Key Points
Active DNA demethylation in mammals is achieved through TET-mediated oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution of oxidized 5mC or thymine DNA glycosylase (TDG)-mediated excision of 5fC and 5caC coupled with base excision repair.
Active DNA demethylation is regulated at various levels, including substrate and cofactor availability, post-transcriptional and post-translational regulation of TET and TDG, and genomic localization of the demethylation machinery.
Studies of tissue distribution, genomic distribution and the dynamics of oxidized 5mC provide insights into the mechanism and function of active DNA demethylation as well as the potential roles of oxidized 5mC.
Active DNA demethylation and oxidized 5mC are involved in pre-implantation embryo development, primordial germ cell development, pluripotency and differentiation, as well as neuronal functions. In certain biological contexts, such as in pre-implantation embryos, the biological meaning of TET-mediated oxidation is not fully understood. In some other biological contexts, such as neurons, the extent of active DNA demethylation and its function require further study.
TET may function in a catalytic-activity-independent manner. Further analysis is needed to distinguish the functions of the TET proteins themselves from the function of active DNA demethylation.
Emerging evidence suggests an interplay between TET, active DNA demethylation and genomic instability and the DNA damage response.
A key mode of regulating DNA methylation is through active demethylation driven by TET-mediated oxidation of 5-methylcytosine (5mC). This Review discusses our latest understanding of the mechanisms and regulation of active DNA demethylation, and the roles of active demethylation (and the oxidized 5mC intermediates) in gene regulation, genome stability, development and disease.
In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation. Additionally, many regulatory mechanisms of this process have been identified. Technological advances in mapping and tracing the oxidized forms of 5mC allow further dissection of their functions. Furthermore, the biological functions of active DNA demethylation in various biological contexts have also been revealed. In this Review, we summarize the recent advances and highlight key unanswered questions.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
