RNA Mediated Transcriptional Gene Silencing: Mechanism and Implications in Writing the Histone Code
Kevin V. Morris
from: RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity (Edited by: Kevin V. Morris). Caister Academic Press, U.K. (2008)
Epigenetics is the study of meiotically and mitotically heritable changes in gene expression which are not coded for in the DNA. Exactly how these epigenetic modifications are directed to the particular gene and the local chromatin has remained enigmatic. Three distinct mechanisms appear to be intricately related and implicated in initiating and/or sustaining epigenetic modifications; DNA methylation, RNA-associated silencing, and histone modifications. Recently we and others have shown in human cells that RNA can specifically direct epigenetic modifications to targeted loci (the promoter regions) and modulate silencing. This regulatory effect is through RNA-associated silencing, can be transcriptional in nature, and is operable through an RNA interference based mechanism (RNAi) that is specifically mediated by the antisense strand of small-interfering RNAs (siRNAs). RNA mediated transcriptional gene silencing, directed DNA methylation as well as the putative mechanism involved in the context of Human cells will be discussed. Undoubtedly, the ramifications from these recent observations represent a paradigm shift in which a hidden layer of complexity is involved in gene regualtion and is operative via the action RNA essentially epigenetically regulating DNA read more ...