How can changes in DNA methylation affect gene expression?

In the context of biological development, DNA methylation serves as a critical epigenetic mechanism that regulates gene expression without altering the underlying genetic sequence. This process involves the enzymatic addition of a methyl group to a cytosine base, typically at CpG dinucleotide sites.1234

DNA methylation affects gene expression primarily through the following mechanisms:

• Transcriptional Repression: Methylation is generally associated with the silencing or "turning off" of genes. It often recruits histone deacetylases, which promote a more condensed, "closed" chromatin structure. This structural change limits the accessibility of the DNA to the transcriptional machinery, such as RNA polymerase and transcription factors, thereby inhibiting gene transcription.413
• Stability of Differentiation: During development, specific methylation patterns help maintain the differentiated state of cells. By stably repressing genes that are not required for a specific cell type, methylation ensures that cells retain their specialized functions through successive cell divisions.1
• Regulatory Control: While often inhibitory, the role of methylation can be complex. For example, in embryonic stem cells, methylation patterns—including non-CpG methylation—are associated with actively transcribed genes, highlighting the dynamic nature of these modifications during early development.3

Aberrant methylation can disrupt these processes, potentially leading to developmental disorders or diseases such as cancer.423