Sequel to Human Genome Released: ENCODE Project Catalogs Regulatory Machinery in DNA

By Saey, Tina Hesman | Science News, October 6, 2012 | Go to article overview

Sequel to Human Genome Released: ENCODE Project Catalogs Regulatory Machinery in DNA


Saey, Tina Hesman, Science News


The human genetic instruction book just got a lot more readable. Nearly a decade after the Human Genome Project assembled the genome's 3 billion chemical units an international consortium has revealed new aspects of genetic grammar.

Already, the updated genome's tales are showing how genetic variants contribute to disease, giving researchers insights into human evolution and even changing how scientists define a gene.

"The questions we can now ask are more sophisticated and will yield better answers than the ones we were asking nine years ago," says Eric Green, director of the National Human Genome Research Institute, which coordinated and funded the mammoth Encyclopedia of DNA Elements, or ENCODE, project.

Results from ENCODE, which involves more than 400 researchers around the globe, appear in the Sept. 6 Nature, with more than 30 companion papers published in Nature, Science, Genome Research, Genome Biology, Cell and BMC Genetics.

When scientists announced the completion of the Human Genome Project in April 2003, researchers could pick out genes that carry instructions for building proteins. But that information equals less than 2 percent of the genome. Some people passed the rest of the genome off as "junk DNA."

"Perhaps none of it is truly junk," says Ross Hardison, a biochemist and molecular biologist at Penn State University in University Park.

The ENCODE analysis reveals that at least 80 percent of the genome may serve some purpose. Within that 80 percent is a complex network of regulatory switches that control how cells interpret the genetic instructions contained in DNA.

The team carefully mapped out more than 4 million short stretches of DNA (usually about six to 10 DNA units, or bases, long) in the genome where proteins called transcription factors latch on, nudging genes' activity up or down. Changes in gene activity help determine how an organism grows and play a role in both health and disease. The scientists also noted places in the genome where DNA or its associated proteins are tagged with certain chemical marks that can change the way DNA is packaged, epigenetic changes that alter gene activity and influence how an organism develops and functions.

Most of the genome appears to be engaged in regulating gene activity, with multiple transcription factors and other regulatory proteins teaming up to control the action of each gene, says John Stamatoyannopolous, a genomics researcher at the University of Washington in Seattle. His team describes complex gene regulatory networks formed by 475 transcription factors in the Sept. …

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Sequel to Human Genome Released: ENCODE Project Catalogs Regulatory Machinery in DNA
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