Final answer:
The modification of DNA that silences gene transcription is methylation of cytosine nucleotides, a key component of epigenetic regulation affecting gene expression.
Step-by-step explanation:
The modification of DNA that can make transcription of a DNA segment unlikely and thus "silence" a gene containing that segment is methylation of cytosine nucleotides.
DNA methylation is a form of epigenetic regulation and involves the addition of a methyl group to the cytosine base within CG pairs, especially in the promoter regions known as CpG islands. This modification can lead to silencing of gene expression because methylated cytosine bases are less accessible for the binding of the necessary transcription machinery, such as RNA polymerase and transcription factors. Highly methylated DNA regions are often associated with deacetylated histones, resulting in tightly coiled chromatin that is transcriptionally inactive. Such epigenetic modifications can be inherited and may be influenced by environmental factors, potentially affecting gene expression patterns across generations. It is also notable that certain cancer cells exhibit a high level of gene silencing through DNA methylation and histone deacetylation, and understanding these epigenetic changes is crucial for developing therapeutic strategies.