ENCODE Decodes DNA
Published Online: Tuesday, September 25, 2012
Andrew L. Pecora, MD
Oncology & Biotech News
Chief Innovations Officer, Professor, and Vice President
of Cancer Services
John Theurer Cancer Center
at Hackensack University
ENCODE analyzed 147 different cell types from the human body using genome sequencing and assessing the functions of RNA and proteins on transcription. The Human Genome Project initially demonstrated that DNA consists of a strand of nearly three billion nucleic acids. It was thought that most of the nucleic acids were inactive or “filler” to connect the portions that were actually read to produce a protein (genes) or promoted reading (promoter regions). The initial surprise arising from the Human Genome Project was that there are only some 20,000 genes in the vast “sea” of nucleic acids making up a DNA strand. The number of “chapters” (genes) readable in a differentiated cell ranges from a low of 22% to a high of 67%. Now, the shocking surprise: the ENCODE project has discerned that the remaining (non-gene) DNA is not largely inactive, but, in “collaboration” with RNA and proteins, acts as signaling switches turning on and off gene transcription. Moreover, unlike the “paltry” 20,000 genes, there are nearly 4 million switches that control the genes.
These transformative findings necessitate a rethinking of “gene-based” diseases, including cancer. In addition to abnormalities in the genes themselves, it is quite likely that in many disease states, the genes are fine and it is the switches that are bad. Clinical benefits derived from work with epigenetic agents supports this contention. In addition to diseases, the field of regenerative medicine may be unleashed by learning more about the relevant switches that control pluripotency.
The great thing about science is how the apple cart of dogma constantly gets turned on its side by new findings. It took Einstein in physics to show Newton the incompleteness of his story in describing the workings of our universe, and now similarly, ENCODE has further illuminated the story of life.
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