5-Hydroxymethylcytosine – the elusive epigenetic mark in mammalian DNA

Abstract

Over the past decade, epigenetic phenomena claimed a central role in cell regulatory processes and proved important factors for understanding complex human diseases. One of the best understood epigenetic mechanisms is DNA methylation. In the mammalian genome, cytosines (C) were long known to exist in two functional states: unmethylated or methylated at the 5-position of the pyrimidine ring (5mC). Recent studies of genomic DNA from the human and mouse brain, neurons and from mouse embryonic stem cells found that a substantial fraction of 5mC in CpG dinucleotides is converted to 5-hydroxymethyl-cytosine (hmC) by the action of 2-oxoglutarate- and Fe(II)-dependent oxygenases of the TET family. These findings provided important clues in a long elusive mechanism of active DNA demethylation and bolstered a fresh wave of studies in the area of epigenetic regulation in mammals. This 15 review is dedicated to critical assessment of the most popular techniques with respect to their suitability for analysis of hmC in mammalian genomes. It also discusses the most recent data on biochemical and chemical aspects of the formation and further conversion of this nucleobase in DNA and its possible biological roles in cell differentiation, embryogenesis and brain function.

Bringing epigenetics into the diagnostics of the andrology laboratory: challenges and perspectives

“…Until now, most of the conventional methods for DNA methylation analysis can distinguish only between methylated and unmethylated cytosine, but not between different kinds of methylation. Thus, methods have been and will be developed to investigate 5-hydroxymethylation 6263. With these new techniques, future studies will be able to elucidate the role of hydroxymethylation in andrology as this DNA modification could also play an essential role in spermatogenesis and embryo development.…”

Evaluation of Anti-HIV-1 Mutagenic Nucleoside Analogues

“…Notably, 5-hydroxymethylcytosine (hm 5 -C), the heterocyclic base of our compound 6, is increasingly being recognized as the sixth base in mammalian DNA (68,69), present at high frequency in CpG dinucleotides. Oxidative damage could lead to the oxidation of 5-methylcytosine (5mC) to hm 5 -C (70), but the conversion also occurs via the Ten-Eleven-Translocation (TET) proteins (71).…”

Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool

“…However, this view is rather oversimplified because additional DNA bases may also be present in most organisms; for example, as a result of epigenetic modifications [1,2] or DNA damage [3]. Chemically-modified bases not only serve as recognition foci for DNA damage response processes, but also for signal transduction.…”