Hydroxylation mediates chromatin demethylation

Methylation of DNA and histones in chromatin has been implicated in numerous biological processes. For many years, methylation has been recognized as static and stable modification, as compared with other covalent modifications of chromatin. Recently, however, several mechanisms have been demonstrated to be involved in demethylation of chromatin, suggesting that chromatin methylation is more dynamically regulated. One chemical reaction that mediates demethylation of both DNA and histones is hydroxylation, catalysed by Fe(II) and alpha-ketoglutarate (KG)-dependent hydroxylase/dioxygenase. Given that methylation of chromatin is an important epigenetic mark involved in fundamental biological processes such as cell fate determination, understanding how chromatin methylation is dynamically regulated has implications for human diseases and regenerative medicine.