Epigenetic Control of Gene Expression

Epigenetic marks control whether RNA polymerase and transcription factors can reach a gene. There are two main mechanisms.1. DNA methylation
A methyl group (CH₃) is added to the base cytosine, usually where cytosine is next to guanine (CpG sites). The enzyme is DNA methyltransferase. Heavy methylation of a gene's promoter stops transcription factors binding and attracts proteins that condense the chromatin, so the gene is switched off. Removing methyl groups can switch it back on.2. Histone modification
DNA is wrapped around histone proteins to form chromatin. Histones are positively charged, so they hold the negatively charged DNA tightly.
• Acetylation: adding acetyl groups to histones reduces their positive charge, so they bind DNA less tightly. The chromatin opens up (euchromatin) and the gene can be transcribed.
• Deacetylation: the enzyme histone deacetylase removes acetyl groups. The chromatin condenses into heterochromatin and the gene is silenced.
Methylation of histones can either activate or repress genes, depending on which amino acid is marked.Short non-coding RNA molecules can also silence genes after transcription by targeting mRNA.These changes explain some diseases. In many cancers, tumour suppressor genes are silenced by methylation of their promoters. Drugs that inhibit DNA methyltransferase or histone deacetylase can switch these genes back on, and some are already used to treat blood cancers.