An important DNA modification is methylation, or the addition of a methyl group to the 5th carbon of cytosine. This forms 5-methylcytosine (5mC), typically associated with repression of gene expression. Reversing this modification requires DNA demethylation, a series of enzymatic reactions which starts with the creation of 5-hydroxymethylcytosine (5hmC).
But 5hmC is not just a transient step in the DNA demethylation pathway but represents an important epigenetic modification in its own right. 5hmC is a key component of the 6-base genome with an essential role in regulating gene expression, maintaining cellular identity, ensuring genomic stability, and responding to environmental changes. Here we explore the unique functions of 5hmC, how it is formed, and highlight its importance in normal development, differentiation, brain function, and its potential as a biomarker in disease pathogenesis.
Image Credit: Biomodal What is DNA demethylation? The DNA demethylation pathway is the biological process through which methyl groups are removed from modified cytosine bases in DNA and is facilitated through either passive or active mechanisms. Passive demethylation occurs when methylation marks are not maintained during DNA replication, leading to a gradual dilution of 5mC with each cell division. Conversely, active demethylation involves the enzymatic removal of methyl groups without the need for DNA replication.
Active DNA demethylation involves a series of enzymatic reactions, primari.