Epigenetic regulation of gene expression

Epigenetic regulation of gene expression refers to the diverse set of mechanisms that control gene activity without altering the underlying DNA sequence. These processes primarily include DNA methylation, histone modifications (such as acetylation and methylation), and chromatin remodeling, which collectively determine the accessibility of DNA to transcriptional machinery (NIH, 2023). By transitioning chromatin between transcriptionally active (euchromatin) and inactive (heterochromatin) states, epigenetic regulators play a critical role in normal development and cellular differentiation (Nature Reviews Genetics, 2016). Dysregulation of these mechanisms is a frequent driver of human diseases, particularly oncology, where aberrant silencing of tumor suppressor genes or activation of oncogenes promotes tumorigenesis and drug resistance. Therapeutic intervention, often termed 'epigenetic therapy,' utilizes small molecules to inhibit 'writers,' 'erasers,' or 'readers' of these epigenetic marks to restore homeostatic gene expression (PubMed, PMC4251029). While highly effective in specific hematological malignancies, the systemic nature of these regulators presents challenges regarding off-target effects and toxicity in non-malignant tissues.

Other names

Epigenetic modificationChromatin remodelingEpigenetic landscapeGene silencingEpigenome regulation

Inhibition of DNA methyltransferases to induce DNA hypomethylation; Inhibition of histone deacetylases to promote gene transcription; Inhibition of histone methyltransferases (e.g., EZH2) to prevent repressive marks; Bromodomain inhibition to prevent 'reading' of acetylated histones.