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.

In human cells 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). 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.

from Kevin V. Morris (2008). RNA Mediated Transcriptional Gene Silencing. In: Morris, K.V. (Ed.) RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press, Norfolk, UK.

Further reading:

1. Epigenetics
2. RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity
3. Molecular Biology Books

Labels: epigenetics, expression, gene regulation, regulation, RNA, RNAi, siRNA

Short RNAs play multiple roles in affecting gene expression at many levels as illustrated by work in Drosophila. RNA interference uses double stranded RNA which is cleaved by Dicer to produce small interfering RNAs (siRNAs) as guides to cleave homologous mRNAs. This process occurs in the cytoplasm and is used in the endogenous process of viral resistance. In addition, many of the same gene products are also involved in transcriptional gene silencing processes. This was first documented for cosuppression of white-Alcohol dehydrogenase transgenes, which is associated with the Polycomb repressive complex of chromatin proteins. Genetic studies of RNA silencing genes also implicate a role in heterochromatin silencing. Some gene products involved in RNAi are also involved in the formation of repeat associated small RNAs (rasiRNAs), whose formation appears to be Dicer independent and critical for repressing transposon expression particularly in the germline. Roles for small RNAs are also implicated in chromatin insulator activity, the integrity of the nucleolus and long-range associations of homeotic genes.

from Kavi et al in RNA and the Regulation of Gene Expression

Labels: Drosophila, regulation, RNA, RNAi, siRNA

Heterochromatin is a prevalent chromatin state among eukaryotes that has critical functions in chromosome segregation, control of genomic stability and epigenetic regulation of gene expression. In the fission yeast Schizosaccharomyces pombe, two RNAi complexes, the RNAi-induced transcriptional gene silencing (RITS) complex and the RNA-directed RNA polymerase complex (RDRC), are part of a RNAi machinery involved in the initiation, propagation and maintenance of heterochromatin assembly. These two complexes localize in a siRNA-dependent manner on chromosomes, at the site of heterochromatin assembly. RNA polymerase II (RNApII) has a central role in RNAi-dependent heterochromatin assembly. RNApII synthesizes a nascent transcript that serves as an RNA platform to recruit RITS, RDRC and possibly other complexes required for heterochromatin assembly. Both RNAi and an exosome-dependent RNA degradation process contribute to heterochromatic gene silencing. Recently reported findings challenge the widely accepted view that heterochromatic gene silencing is caused strictly by chromatin compaction. As RNAi-dependent chromatin modifications have been observed throughout the eukaryotic kingdom the mechanisms described here may be utilized in a large range of eukaryotes.

from Vavasseur et al in RNA and the Regulation of Gene Expression

Further reading: Epigenetics

Labels: epigenetics, regulation, RNA, RNAi, siRNA, yeast