Demethylation
Demethylation is a biochemical process involving the removal of a methyl group (CH₃) from a molecule. This process is crucial in the regulation of gene expression, protein function, and cellular signaling.
Mechanism[edit | edit source]
Demethylation can occur through various mechanisms, including:
- Oxidative demethylation: This involves the oxidation of the methyl group, often mediated by enzymes such as cytochrome P450.
- Hydrolytic demethylation: This involves the addition of a water molecule to break the bond between the methyl group and the rest of the molecule.
- Enzymatic demethylation: Specific enzymes, such as DNA demethylase and histone demethylase, catalyze the removal of methyl groups from DNA and histones, respectively.
Biological Significance[edit | edit source]
Demethylation plays a critical role in various biological processes, including:
- Gene expression: Demethylation of DNA and histones can activate or repress gene expression. For example, the demethylation of CpG islands in gene promoters is often associated with gene activation.
- Epigenetic regulation: Demethylation is a key mechanism in epigenetics, influencing cell differentiation, development, and disease.
- Protein function: Demethylation of proteins can alter their function, stability, and interactions with other molecules.
Enzymes Involved[edit | edit source]
Several enzymes are involved in demethylation, including:
- TET enzymes: These enzymes oxidize 5-methylcytosine in DNA to facilitate its removal.
- LSD1 (lysine-specific demethylase 1): This enzyme demethylates histones, affecting chromatin structure and gene expression.
- JmjC domain-containing proteins: These are a family of histone demethylases that require Fe(II) and α-ketoglutarate for their activity.
Clinical Relevance[edit | edit source]
Aberrant demethylation is associated with various diseases, including:
- Cancer: Abnormal DNA demethylation can lead to the activation of oncogenes or the silencing of tumor suppressor genes.
- Neurological disorders: Dysregulation of demethylation processes is implicated in conditions such as Alzheimer's disease and schizophrenia.
- Autoimmune diseases: Altered demethylation patterns can contribute to the pathogenesis of diseases like systemic lupus erythematosus.
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Contributors: Prab R. Tumpati, MD