3Qs: New clues to unlocking the genome

Last week, Nature ²Ñ²¹²µÂ²¹Â³ú¾±²Ô±ð, Genome Research and Genome Biology pubÂlished 30 papers on breakÂthrough research that will change the face of genetics. After nearly a decade of searching, the EncyÂcloÂpedia of DNA EleÂments (ENCODE) ConÂsorÂtium has assigned bioÂchemÂical funcÂtions to 80 perÂcent of the genome. PreÂviÂously conÂsidÂered "junk," the develÂopÂment adds sigÂnifÂiÂcant insight into the imporÂtance of the nonÂcoding regions of DNA. We asked Veronica Godoy-​​Carter, assisÂtant proÂfessor of biology, to explain.
What is noncoding DNA and why has it been called "junk"?
The genetic mateÂrial present in all living organÂisms is DNA. It is underÂstood that "coding" DNA can be "read" by the celÂlular machinery, as we read a page in a book, mostly as proÂteins (e.g., your hair and nails are made up of proÂteins). HowÂever, there are secÂtions of the DNA in metaÂzoans (e.g., humans) and in some uniÂcelÂlular organÂisms known to have no readÂable code, that is, nonÂcoding DNA. The word "junk" was used in the 14th cenÂtury to denote an old or infeÂrior rope. Today it is used to charÂacÂterize useÂless artiÂcles or those of little value. Thus, when researchers started to deciÂpher the linear sequence of the DNA, it became obvious that a large fracÂtion of it is nonÂcoding. ThereÂfore, the word "junk" was used to describe such nonÂcoding regions.
We've known for a while that noncoding DNA actually has very important physiological functions. How does this new research change or add to that understanding?
has shown that, conÂtrary to preÂvious views, most of the sequences of the human genome are not useÂless. Though it was preÂviÂously known than nonÂcoding regions were imporÂtant for regÂuÂlaÂtion, this project has demonÂstrated that nonÂcoding sequences serve as a roadmap for regÂuÂlaÂtory DNA binding proÂteins that effect expresÂsion of coding regions. PreÂvious to this large-​​scale analysis, no one knew about the extent of regÂuÂlaÂtory regions that existed in "junk" DNA, now referred to as "dark matter." For example, there are many sites that are specifÂiÂcally chemÂiÂcally modÂiÂfied, perÂmitÂting inhiÂbiÂtion or inducÂtion of the DNA coding regions. RemarkÂably, the regÂuÂlaÂtion of expresÂsion does not only occur in coding regions that are adjaÂcent to regÂuÂlaÂtory eleÂments, as preÂviÂously thought. In some cases, regÂuÂlaÂtion is long range and seems to occur only when the regÂuÂlaÂtory eleÂments are near coding regions in the three-​​dimensional space!
How will this new understanding of noncoding DNA change the face of genetic research?
The long-​​range regÂuÂlaÂtion of coding regions in the DNA is such an exciting finding because it will permit us to start underÂstanding the effect of known changes in the DNA sequence (i.e., mutaÂtions) between, say, healthy and cancer tisÂsues. As it turns out, many mutaÂtions assoÂciÂated with disÂease are in nonÂcoding regions, which preÂviÂously made little sense. Now it will be posÂsible to map mutaÂtions on this roadmap and imporÂtantly it will be posÂsible to underÂstand how mutaÂtions far away in the linear DNA change the regÂuÂlaÂtory landÂscape of cells.
Journal information: Nature , Genome Research , Genome Biology
Provided by Northeastern University