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The DNA methylome refers to the comprehensive set of cytosine methylation modifications across the entire genome of a cell [1]. It primarily involves the addition of a methyl group to the 5-carbon of cytosine residues within CpG dinucleotides, serving as a fundamental epigenetic mechanism for controlling gene expression [2]. High levels of methylation in promoter regions typically correlate with transcriptional silencing, which is essential for normal development, genomic imprinting, and X-chromosome inactivation [2]. In pathological states, particularly oncology, the methylome often undergoes massive reorganization characterized by global hypomethylation and focal hypermethylation of tumor suppressor genes [3]. While the methylome itself is a genomic state rather than a single protein target, it is therapeutically modulated using DNA methyltransferase (DNMT) inhibitors like azacitidine and decitabine to reverse aberrant silencing [4]. These drugs incorporate into DNA and trap DNMT enzymes, resulting in a loss of methylation during subsequent rounds of cell division [4].
Inhibition of DNA methyltransferases (DNMTs), leading to global DNA hypomethylation and the reactivation of epigenetically silenced genes [4].
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