The Epigenetic Insights of RNA-Seq

May 2, 2016
The Epigenetic Insights of RNA-Seq
RNA species help regulate gene expression transcriptionally and post-transcriptionally. At the transcriptional level, as suggested by this image, RNA species can modify chromatin structure and mediate the recruitment of histone and DNA methyltransferases, leaving different stretches of DNA more or less ready for expression. At the post-transcriptional level, RNA species can, if acted upon by Dicer and Argonaut, contribute guide strands to the RNA-induced silencing complex, or RISC, enabling RISC to cleave messenger RNA in a sequence-specific manner. [National Institute of Environmental Health Sciences]

Jeffrey S. Buguliskis, Ph.D.

DNA→RNA→Protein. This flow of genetic information has been the framework of modern biology since it was first enunciated by Francis Crick in 1958. However, in recent years researchers have begun to assemble a more comprehensive picture surrounding the “central dogma” of molecular biology, leading to the revelation that RNA is not just a simple genetic messenger—a middleman so to speak—but rather a complex signaling molecule that is present in an ever increasing number of structural forms. The various iterations in which RNA exists allow the molecule to act as the template for translating the genetic code into protein, as a gene silencer and post-transcriptional regulator of gene expression, and, as most recently discovered, a modulator of epigenetic elements.

In a search to understand human development better at the molecular level, Conrad H. Waddington, coined the term “epigenetics” in 1942, to describe the influence of genetics on developmental processes. Decades later scientists discovered that environmental factors caused heritable phenotypic changes in fruit flies that did not change the underlying DNA sequence—in essence, a change in phenotype without a change in genotype. 

Epigenetic regulation represents an important driver of diversity within populations of various species and can be influenced by several factors, including age, disease state, and the environment in which a species lives. These various influences can lead to characteristic changes in organisms, such as guiding undifferentiated cells toward their final form. However, epigenetic mechanisms can also go awry and result in damaging effects, leading to the development of disease states like cancer.

Currently, investigators are pursuing three main pathways that are used by cells to bring about and maintain epigenetic changes: DNA methylation, modifications of core nucleosome proteins called histones, and gene silencing through noncoding RNA (ncRNA). In-depth analysis of these pathways is the research objective of many laboratories, with changes in DNA methylation currently representing the lion’s share of the knowledge base for epigenetics. However, many scientists are beginning to take notice of the potential influence ncRNAs have on epigenetic regulation, especially when it comes to the onset of diseases such as cancer.

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