Abstract
DNA methylation is an abundant and stable epigenetic modification that allows inheritance of information from parental to daughter cells. At active genomic regions, DNA methylation can be reversed by TET (Ten-eleven translocation) enzymes, which are responsible for fine-tuning methylation patterns. TET enzymes oxidize the methyl group of 5-methylcytosine (5mC) to yield 5-hydroxymethylcytosine (5hmC) and other oxidized methylcytosines, facilitating both passive and active demethylation. Increasing evidence has demonstrated the essential functions of TET enzymes in regulating gene expression, promoting cell differentiation, and suppressing tumor formation. In this review, we will focus on recent discoveries of the functions of TET enzymes in the development and function of lymphoid and myeloid cells. How TET activity can be modulated by metabolites, including vitamin C and 2-hydroxyglutarate, and its potential application in shaping the course of immune response will be discussed.
Highlights
Cells rely on the proper propagation and preservation of epigenetic information in order to regulate gene expression appropriately. 5-methylcytosine (5mC), described as the 5th base of DNA, is a chemically stable modification that is one of the most reliable ways of transmitting epigenetic information
During DNA replication, methylated CGs are replaced by unmodified cytosines in the newly synthesized DNA strand, and the resulting hemimethylated CGs are recognized by a complex of UHRF1 and the maintenance methyl-transferase DNMT1 [2,3,4]
In contrast to DNMT1, which depends on 5mC deposition at CpG motifs for maintenance DNA methylation, the de novo methyltransferases DNMT3A and DNMT3B can methylate unmodified cytosines in both CG and CH sequence contexts
Summary
Cells rely on the proper propagation and preservation of epigenetic information in order to regulate gene expression appropriately. 5-methylcytosine (5mC), described as the 5th base of DNA, is a chemically stable modification that is one of the most reliable ways of transmitting epigenetic information. Besides being a potential epigenetic mark, 5hmC is the key intermediate for TET-mediated active (replication-independent) and passive (replication-dependent) DNA demethylation (Figure 1). DNA modification by TET proteins is essential for gene regulation (Figure 2).
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