Cytosine hydroxymethylation by TET enzymes: From the control of gene expression to the regulation of DNA repair mechanisms, and back

Abstract

Chromatin is a complex multi-scale structure composed of DNA wrapped around nucleosomes. The compaction state is finely regulated mainly by epigenetic marks present not only on nucleosomes but also on the DNA itself. The most studied DNA post-transcriptional modification is 5-methylcytosine (5-mC). Methylation of the cytosine at CpG islands localized at the promoter is associated with repression of transcription. On the contrary, enrichment of 5-hydroxymethylcytosine (5-hmC), one of the oxidation products of 5-mC by TET (ten-eleven translocation) enzymes, on promoters and enhancers promotes transcription activation. Recently, a new role of 5-hmC has been proposed in the context of DNA repair. 5-hmC was found to be enriched at DNA lesions and knockdown of TET led to impaired repair efficiency. Here, we review our current knowledge regarding the role of the regulation of the 5-mC/5-hmC balance by TET enzymes in the context of transcription modulation as well as DNA repair processes. In a final section, we speculate on the potential involvement of TET proteins in DNA repair mechanisms associated with transcription activation.

Keywords

• chromatin
• DNA repair
• transcription
• ten eleven translocation
• 5-hydroxymethylcytosine