DNA methylation is the addition of a methyl group (-CH3) to a cytosine base in DNA. It is one of the main epigenetic marks and usually switches genes off.Where it happens
Methylation usually occurs where a cytosine is followed by a guanine in the base sequence. These sites are called CpG sites. Clusters of CpG sites, called CpG islands, are common in the promoter regions of genes. The methyl groups are added by enzymes called DNA methyltransferases. The base sequence is not changed: the cytosine is still read as cytosine.
How it silences a gene
When the promoter of a gene is heavily methylated:
• the methyl groups prevent transcription factors and RNA polymerase from binding to the promoter
• proteins that recognise methylated DNA bind to it and attract enzymes that cause the chromatin to become more tightly packed.
So the gene is not transcribed. Unmethylated promoters allow transcription.Maintenance through cell division
After DNA replication, each new double helix has one methylated old strand and one unmethylated new strand. A maintenance methyltransferase recognises this and methylates the matching cytosines on the new strand. This means methylation patterns are copied to daughter cells, so a specialised cell's pattern of silenced genes is passed on.Examples
• In female mammals, one X chromosome in each cell is inactivated, and methylation helps keep it silent.
• In some cancers, the promoters of tumour suppressor genes become heavily methylated (hypermethylated). The genes are switched off, so cell division is no longer controlled, even though the genes themselves have no mutation.
Methylation usually occurs where a cytosine is followed by a guanine in the base sequence. These sites are called CpG sites. Clusters of CpG sites, called CpG islands, are common in the promoter regions of genes. The methyl groups are added by enzymes called DNA methyltransferases. The base sequence is not changed: the cytosine is still read as cytosine.
How it silences a geneWhen the promoter of a gene is heavily methylated:
• the methyl groups prevent transcription factors and RNA polymerase from binding to the promoter
• proteins that recognise methylated DNA bind to it and attract enzymes that cause the chromatin to become more tightly packed.
So the gene is not transcribed. Unmethylated promoters allow transcription.Maintenance through cell division
After DNA replication, each new double helix has one methylated old strand and one unmethylated new strand. A maintenance methyltransferase recognises this and methylates the matching cytosines on the new strand. This means methylation patterns are copied to daughter cells, so a specialised cell's pattern of silenced genes is passed on.Examples
• In female mammals, one X chromosome in each cell is inactivated, and methylation helps keep it silent.
• In some cancers, the promoters of tumour suppressor genes become heavily methylated (hypermethylated). The genes are switched off, so cell division is no longer controlled, even though the genes themselves have no mutation.