title: High-throughput sequencing offers new insights into 5-hydroxymethylcytosine.
abstract: Chemical modifications of DNA comprise epigenetic mechanisms that contribute to the maintenance of cellular activities and memory. Although the function of 5-methylcytosine (5-mC) has been extensively studied, little is known about the function(s) of relatively rarer and underappreciated cytosine modifications including 5-hydroxymethylcytosine (5-hmC). The discovery that ten-eleven translocation (Tet) proteins mediate conversion of 5-mC to 5-hmC, and other oxidation derivatives, sparked renewed interest to understand the biological role of 5-hmC. Studies examining total 5-hmC levels revealed the highly dynamic yet tissue-specific nature of this modification, implicating a role in epigenetic regulation and development. Intriguingly, 5-hmC levels are highest during early development and in the brain where abnormal patterns of 5-hmC have been observed in disease conditions. Thus, 5-hmC adds to the growing list of epigenetic modifications with potential utility in clinical applications and warrants further investigation. This review discusses the emerging functional roles of 5-hmC in normal and disease states, focusing primarily on insights provided by recent studies exploring the genome-wide distribution of this modification in mammals.
authors.forename: Alina P S
authors.initials: AP
authors.lastname: Pang
authors.forename: Christopher
authors.initials: C
authors.lastname: Sugai
authors.forename: Alika K
authors.initials: AK
authors.lastname: Maunakea
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009928:Organ Specificity / Q000235:genetics
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine