Since the sequencing of the human and other genomes in the 1990s, it has been recognized that large sections of the genome did not appear to be coding for genes that produced protein products. This observation earned these regions the unfortunate title of “junk DNA”. Recent studies, however have put to rest the notion that organisms cart around a load of useless DNA sequences. It is now evident that these megabases of DNA are essential for controlling the flow of genetic information, and that these regions carry networks of epigenetic and genetic regulatory genes coordinating this activity.
A slew of papers published simultaneously in Nature and Science have revealed the complexity of the genome’s regulatory networks. Starting in 2003, the ENCODE project revealed that 76% of the genome is transcribed into RNA molecules that do not translate into proteins. These RNAs are involved gene regulation by combining with and blocked specific messenger RNA molecules. These regulatory RNA molecules travel to different sites within the cell where they exert their controlling influences.
In addition, the researchers identified genes that code for regulatory proteins that influence gene activity by binding to specific sites within the DNA. These proteins frequently exert their regulatory power by binding to the histones, a class of DNA-associated proteins that form part of the epigenome.
While these studies are building an understanding genetic regulation and its complexities in humans, they are also aiding in our analysis of disease processes. The investigators identified many genetic regulatory variants related to diseases such as diabetes, bipolar disorder, Parkinson’s disease and lupus. The researchers further state that they have uncovered regulatory DNA variation in a variety of pathological states, revealing important insights into the origins of these conditions.
The understanding genomic and epigenomic regulatory networks in human disease represents a new paradigm and a basis for the development of radical new drug therapies.
A more detailed look at the role of epigenetics in clinical medicine and epigenetics in drug discovery is the subject of a recent Kalorama report, Epigenetics, a complete market research survey of the nascent epigenetic industry authored by K. John Morrow, Jr. PhD.