Reversible methyl modifications in DNA and RNA: dynamics in stem cell growth and differentiation.

A broad repertoire of modifications is known to underlie adaptable coding and structural function of proteins, DNA and various RNA species. Methylations of mammalian DNA and histone residues are known to regulate transcription and the discoveries of demet hylases that remove methylation in DNA and histones provide a basis for the understanding of dynamic regulation of mammalian gene expression. In mRNA, the m6A modification is particularly interesting since it is the most abundant internal modification and was recently shown to be reversible in a reaction similar to the hydroxylation of 5-methylcytosine (5mC) to 5hmC in DNA. The discovery of these demethylases has led to a tremendous progress in the understanding of methyl marks in gene regulation and role in numerous diseases. Here, we propose to study the reversible methyl modifications on DNA and RNA and their dynamics in stem cell growth and differentiation. We aim to follow a similar approach for studying the dynamics of 5hmC and m6A, and thus, create exciting interaction between the post doc and the PhD student, their supervisors and international collaborators.