Unmethylation

Unmethylation refers to the process of removing a methyl group from a molecule. In molecular biology, this most commonly refers to the removal of a methyl group from DNA, a process known as demethylation. DNA methylation is a crucial epigenetic modification that plays a significant role in gene regulation, silencing gene expression by altering the structure of chromatin. Unmethylation, or demethylation, is the reversal of this process.

Active DNA demethylation is an enzymatic process that involves a series of oxidation and base excision repair steps. Key enzymes involved in active demethylation include TET (ten-eleven translocation) proteins, which oxidize 5-methylcytosine to 5-hydroxymethylcytosine, and subsequent modifications that lead to the removal of the modified base and its replacement with an unmethylated cytosine. Passive demethylation occurs during DNA replication when maintenance DNA methyltransferases fail to re-establish methylation marks on the newly synthesized strand, leading to a dilution of methylation over successive cell divisions.

Unmethylation is essential for various biological processes. It is critical for normal development, allowing for the dynamic regulation of gene expression required for cell differentiation and tissue formation. It also plays a role in cellular plasticity, enabling cells to switch gene expression patterns in response to environmental cues. Aberrant unmethylation patterns have been implicated in a variety of diseases, including cancer, where inappropriate gene activation due to demethylation can lead to uncontrolled cell growth. Understanding unmethylation is therefore vital for comprehending gene regulation and disease pathology.