DNA demethylation is the removal of methyl groups from cytosine bases in DNA. It reverses DNA methylation, so a gene that had been silenced can be switched back on.How it happens
• Passive demethylation: if the maintenance methyltransferase is inactive when DNA replicates, the new strands are not methylated. With each round of cell division, the proportion of methylated DNA halves.
• Active demethylation: enzymes chemically modify the methyl groups on cytosines and the modified bases are then replaced with ordinary cytosine. This can happen without cell division.Effect on gene expression
When the methyl groups are removed from a promoter, transcription factors and RNA polymerase can bind again and the chromatin can become less tightly packed, so the gene can be transcribed.Reprogramming in development
Most methylation marks are removed shortly after fertilisation, so the cells of the early embryo can express the genes needed to form any type of cell. New patterns of methylation are then added as cells differentiate. Methylation is also erased and reset in the cells that will become eggs and sperm.Demethylation and disease
In many cancers, large parts of the genome lose their methylation (hypomethylation). This can switch on oncogenes that promote cell division and make chromosomes unstable.Because methylation can be removed, some cancer drugs work by blocking DNA methyltransferases, so that tumour suppressor genes silenced by methylation lose their methyl groups as cells divide and are switched back on.
• Passive demethylation: if the maintenance methyltransferase is inactive when DNA replicates, the new strands are not methylated. With each round of cell division, the proportion of methylated DNA halves.
• Active demethylation: enzymes chemically modify the methyl groups on cytosines and the modified bases are then replaced with ordinary cytosine. This can happen without cell division.Effect on gene expression
When the methyl groups are removed from a promoter, transcription factors and RNA polymerase can bind again and the chromatin can become less tightly packed, so the gene can be transcribed.Reprogramming in development
Most methylation marks are removed shortly after fertilisation, so the cells of the early embryo can express the genes needed to form any type of cell. New patterns of methylation are then added as cells differentiate. Methylation is also erased and reset in the cells that will become eggs and sperm.Demethylation and disease
In many cancers, large parts of the genome lose their methylation (hypomethylation). This can switch on oncogenes that promote cell division and make chromosomes unstable.Because methylation can be removed, some cancer drugs work by blocking DNA methyltransferases, so that tumour suppressor genes silenced by methylation lose their methyl groups as cells divide and are switched back on.