Gene Silencing and DNA Methylation

This review revealed a new mechanism for gene regulation through “gene silencing” at the transcriptional level (TGS) or at the posttranscriptional level (PTGS), which play a key role in many essential cellular processes. TodayRNA is used as a powerful tool to experimentally elucidate the function of essentially any gene in a cell. The immense impact of the discovery of RNA interference (RNAi) on biomedical research and its novel medical applications in the future are reviewed in this article, with particular stress on therapeutic applications of radio-labeled antisense oligonucleotides (RASONs) for diagnosis and treatment of various cancers and neurodegenerative diseases by “gene silencing”. Antisense oligonucleotides (ASONs) can also modulate alternative splicing which 74% of all human genes undergo. Epigenetic changes affect chromatin structure and thus regulate processes such as transcription, X-chromosome inactivation, allele-specific expression of imprinted genes, and inactivation of tumor suppressor genes. Treatment with inhibitors of DNA methylation and histone deacetylation can reactivate epigenetically silenced genes and has been shown to restore normal gene function. In cancer cells, this results in expression of tumor suppressor genes and other regulatory functions, inducing growth arrest and apoptosis.

Author(s): P. Parveen, K. Deepti Brundavani, K. Mahathi, M.S. Bhavani and SK. Shaheda Sultana

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