Vol. 7, Issue 1, Part A (2025)

Epigenetic regulation plays a critical role in controlling gene expression without altering the underlying DNA sequence. Among the various epigenetic mechanisms, histone modifications and DNA methylation are pivotal in modulating chromatin structure and gene accessibility. This review paper focuses on the trimethylation of histone H3 at lysine 27 (H3K27me3) and its interplay with DNA methylation. H3K27me3, catalyzed by the Polycomb Repressive Complex 2 (PRC2), is a well-characterized repressive mark that contributes to transcriptional silencing during development and in disease states such as cancer. DNA methylation, mainly occurring at CpG dinucleotides, is another essential epigenetic mark involved in stable gene repression and genomic imprinting. Together, these modifications coordinate a robust system of gene regulation that ensures cellular identity and function. This paper discusses the molecular machinery behind these modifications, their functional roles, crosstalk mechanisms, and implications in human diseases, offering insights into emerging epigenetic therapies.