5-hydroxymethylcytosine: a new insight into epigenetics in cancer

Abstract

DNA methylation at the 5 position of cytosine (5-mC) has emerged as a key epigenetic marker that plays essential roles in various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family proteins, which is now widely recognized as the "sixth base" in the mammalian genome, following 5-mC, the "fifth base". 5-hmC is detected to be abundant in brain and embryonic stem cells, and is also distributed in many different human tissues. Emerging evidence has shown that 5-hmC and TET family might serve unique biological roles in many biological processes such as gene control mechanisms, DNA methylation regulation, and involved in many diseases, especially cancers. In this paper we provide an overview of the role of 5-hmC as a new sight of epigenetics in human cancer.

Keywords: 5-hmC; DNA methylation; TET; cancer; epigenetics.

Figure 1. The relationship between 5-mc and 5-hmC. 5-mC is formed by post-replicative addition of methyl group to cytosine through the action of DNA methyltransferase (DNMT) which using S-adenosyl methionine (SAM) as methyl donor. Tet family proteins (TET1/2/3) catalyze 5-mC oxidation to 5-hmC in the presence of O₂ and iron, 5-hmC can be further oxidized mainly to 5-fC and 5-caC. 5-hmC can be converted to 5-hmU via activation-induced deaminase (AID), which in turn can be converted to cytosine following base-excision repair (BER) pathway-mediated demethylation.