How erasure of DNA methylation works at the molecular level has been a mystery for many years, however recently it has been found that the methylated cytosine can be further modified by so-called deaminases and hydroxylases, and eventually removed during DNA replication or by DNA repair. Our studies have shown that deaminases and hydroxylases are indeed involved in genome-wide demethylation in PGCs and in the zygote, respectively.
We have also carried out one of the first genome-wide mapping study of hydroxymethylation in ES cells, which has revealed continuous reprogramming of methylation patterns in these pluripotent cells which is likely associated with their plasticity and ability to reprogramme somatic cells. We have recently discovered signaling pathways in ES cells which regulate genome-wide epigenetic reprogramming, including through controlling methylases and demethylases.
We have also recently initiated work on epigenetic regulation of social behaviours in insects, where we are interested in how patterning and regulation of DNA methylation in the brain is linked with the evolution of sociality. We expect that on-going and future work will take us closer to the heart of these remarkable epigenetic dynamics and its roles in reprogramming, pluripotency, transgenerational inheritance, ageing, and behaviour.
The figure shows overall relative distribution of 5-methylcytosine (5mC-red) and 5-hydroxymethylcytosine (5hmC-green) across genes in mouse ES cells. 5hmC near the transcription start site may help maintain low 5mC levels and thus ES cell plasticity. The upper panel depicts simultaneous immunofluorescence staining of a colony of ES cells with 5mC (red), 5hmC (green) and DAPI (blue).