Regulatory impact of activating and inactivating histone modifications for epigenetic control of Tet expression during murine brain development and aging

Background: Recent studies demonstrated that 5-hydroxymethylcytosine (5hmC) is particularly enriched in the brain. It is the oxidative product of 5-methylcyotsine (5mC), mediated by the ten-eleven translocation (Tet) genes. Being the intermediate in DNA demethylation, 5hmC itself may also be regulated by certain chromatin structures. As there is an unknown biological mechanism in murine brain and other tissues, there is a need to investigate the biological mechanisms linking 5hmC formation and histone modifications. The aim of this study was to check up the regulation levels of quantified expression levels of genes that are associated with DNA demethylation in murine brain during aging at regions with the histone modifications H3K4me3 (a euchromatin mark) and H3K27me3 (a transcription repressive mark). Results: We show significant reduction of expression levels of the Tet genes compatible for regulation levels at H3K27me3. H3K4me3 displays relatively strong correlations with still known quantified 5hmC amounts in cortex and in cerebellum. Conclusions: Our results demonstrate a new insight into 5hmC availability depending on transcriptional activity and into Tet gene expressions depending on transcriptional repression.