Demethylase

Enzyme that removes methyl groups from molecules

Demethylase

Demethylases are a class of enzymes that remove methyl groups from methylated molecules, a process known as demethylation. These enzymes play a crucial role in the regulation of gene expression, epigenetic modifications, and the metabolism of various compounds within the cell.

Function

Demethylases are involved in the removal of methyl groups from DNA, RNA, and histones, which are proteins that help package DNA into chromatin. This process is essential for the regulation of gene expression, as methylation typically acts to repress gene activity. By removing methyl groups, demethylases can activate genes that were previously silenced.

DNA Demethylation

DNA demethylation is a critical process in epigenetics, where demethylases remove methyl groups from cytosine bases in DNA. This can lead to the reactivation of genes that are important for development and differentiation. The TET family of enzymes is known to play a significant role in DNA demethylation.

Histone Demethylation

Histone demethylases remove methyl groups from lysine and arginine residues on histone proteins. This modification can alter the chromatin structure and influence gene expression. The LSD1 and JmjC domain-containing families are well-known histone demethylases.

Types of Demethylases

Demethylases can be broadly categorized based on their substrate specificity and the type of methylation they reverse. Some of the major types include:

• DNA Demethylases: Enzymes like TET1, TET2, and TET3 that are involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, leading to DNA demethylation.
• Histone Demethylases: Enzymes such as LSD1 (lysine-specific demethylase 1) and the JmjC domain-containing demethylases, which remove methyl groups from histone proteins.

Mechanism

Demethylases typically function by oxidizing the methyl group, which can then be removed as formaldehyde or further processed. The specific mechanism can vary depending on the type of demethylase and its substrate.

Clinical Significance

Aberrant demethylation is associated with various diseases, including cancer, neurological disorders, and autoimmune diseases. Understanding the role of demethylases in these conditions can lead to the development of targeted therapies.

Research and Applications

Research into demethylases is ongoing, with a focus on understanding their role in normal physiology and disease. Inhibitors of specific demethylases are being explored as potential therapeutic agents in cancer and other diseases.

Also see

• Methylation
• Epigenetics
• Histone modification
• Gene expression
• TET enzymes

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  Lysine demethylation process
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  Jmjd2a structure with domains highlighted
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  Lysine specific demethylase 1
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  1a2o structure
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  Chemotaxis regulation within E. coli