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

Designed molecules that recognize specific sequences within chromosomal DNA could provide useful probes for natural cellular processes, tools for laboratory experimentation, and lead compounds for therapeutic development. It was discovered that duplex DNA could be recognized by conjugates consisting of DNA oligonucleotides and cationic proteins or peptides. Similarly efficient recognition by neutral peptide nucleic acids (PNAs) was observed. It was found that duplex RNAs could also mediate efficient recognition of duplex DNA. RNAs can target transcription start sites and either inhibit or activate gene expression. This indicates that promoter-targeted RNAs can be powerful tools for regulating gene expression.

from Corey, DR (2008) RNA-Mediated Recognition of Chromosomal DNA. In: Morris , K.V. (Ed.) RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press, Norfolk, UK.

Labels: expression, gene regulation, PNA, promoter, regulation, RNA, therapeutics

A pyknon is a new type of putative regulatory motif that named from the greek adjective for dense. By definition, pyknons are variable length sequences with a statistically significant number of intact copies in the intergenic and intronic regions of the genome and additional copies in the untranslated or amino acid coding regions of known transcripts. Even though the original presentation discussed pyknons in the context of the human genome, pyknons likely represent a more general architectural component of eukaryotic genomes. The exact role of pyknons is currently unclear but the findings so far support a regulatory responsibility. The possibility has been raised that pyknons hint at a previously unseen layer of cell process regulation.

from Rigoutsos, I (2008) Pyknons as putative novel and organism-specific regulatory motifs In: Morris , K.V. (Ed.) RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Caister Academic Press, Norfolk, UK.

Labels: gene regulation, pyknon, regulation, RNA

MicroRNAs are short, ~22 nucleotide regulatory RNAs, first discovered in Caenhorhabditis elegans. Hundreds of microRNAs have been identified in plants and animals. Based on the current number of predicted microRNAs, one to three percent of genomic DNA is believed to encode these small, regulatory RNAs.

MicroRNAs inhibit protein synthesis by binding to their target mRNAs and regulating gene expression in a post-transcriptional manner. The exact mechanism by which target gene expression is down-regulated is unclear; however, experimental evidence has led to several different theories to explain microRNA-mediated mRNA repression. These possible mechanisms include target degradation, localization to P-bodies, inhibition of translation initiation or elongation, mRNA deadenylation, and mRNA destabilization.

from Chin and Slack in RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity

Further reading: RNA and the Regulation of Gene Expression

Labels: gene regulation, microRNA, mRNA, regulation, RNA