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Chapter 15: Problem 17

What is the mechanism by which the chemical 5-azacytidine enhances gene expression?

Short Answer

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Question: Explain the mechanism by which 5-azacytidine enhances gene expression. Answer: 5-azacytidine is a DNA demethylating agent that enhances gene expression by reducing methylation. It gets incorporated into the DNA during replication, forming covalent adducts with DNA methyltransferases and inactivating them. This prevents the addition of methyl groups to cytosine residues in CpG dinucleotides, leading to DNA demethylation. The demethylation process opens the DNA's structure, allowing transcription factors to bind more easily and activate previously silenced genes, resulting in overall enhanced gene expression.

Step by step solution

01

Introduction to 5-azacytidine

5-azacytidine is a chemical compound that acts as a DNA demethylating agent. It is used in research and medical applications to alter gene expression, primarily by reducing methylation.
02

Understanding DNA methylation

DNA methylation is a process that involves the addition of a methyl group (CH3) to the DNA molecule, typically at the cytosine residue in a CpG dinucleotide. This process usually results in the repression of gene expression, as it changes the DNA's structure and accessibility to transcription factors.
03

5-azacytidine's mode of action

5-azacytidine gets incorporated into the DNA during replication. Once incorporated, it forms covalent adducts with DNA methyltransferases, the enzymes responsible for DNA methylation. This process inactivates the DNA methyltransferases, preventing the addition of methyl groups to cytosine residues in the CpG dinucleotides.
04

Demethylation process

With the DNA methyltransferases inactivated, the DNA undergoes demethylation. This means that the previously methylated CpG dinucleotides lose their methyl groups. As a result, the DNA's structure becomes more open and accessible to transcription factors.
05

Enhancement of gene expression

The demethylation process allows transcription factors to bind to the DNA more easily, enabling the activation of previously silenced genes. This results in an overall enhancement of gene expression.
06

Applications of 5-azacytidine

5-azacytidine is used in research to study the effects of DNA methylation on gene expression and may also be used as a cancer treatment in some cases, such as for myelodysplastic syndromes, due to its ability to reactivate tumor suppressor genes that have been silenced by methylation.

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