Monthly Archives: September 2013

Public release date: 18-Sep-2013 [ | E-mail | Share ]

Contact: Craig Boerner craig.boerner@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Using technology he helped develop, Vanderbilt University scientist Bryan Venters, Ph.D., has shed new light on the "dark matter" of the genome and has begun to explore a possible new approach to treating cancer.

"Clarity is everything," said Venters, assistant professor of Molecular Physiology and Biophysics who further developed the high-resolution technology as a postdoctoral fellow in the lab of Frank Pugh, Ph.D., at Pennsylvania State University before moving to Vanderbilt in January.

Venters and Pugh are co-authors of a paper published this week in the journal Nature that describes their finding.

Much of the DNA of the human genome has been called "dark matter" because only a tiny fraction, about 3 percent, makes up the approximately 20,000 protein-coding genes that are transcribed into RNA copies, and then translated into proteins.

Other parts of the genome are transcribed into non-coding RNA, presumably to perform other functions, but until recently the origin of this non-coding RNA was unknown.

Now, with a technique called ChIP-exo developed at Penn State that identifies protein-DNA interactions at near base-pair resolution, Venters and Pugh have shown that so-called transcription initiation complexes drive much of the non-coding transcription occurring throughout the genome.

In a model leukemia cell line, they discovered about 150,000 complexes along non-coding stretches of the DNA the most ever discovered. This suggests, they concluded, that "pervasive non-coding transcription is promoter-specific, regulated, and not that much different from coding transcription (of genes)."

Venters compared the technique to the highly sensitive satellite cameras that enable web-based map applications to zoom in from a continental view to street level, "and tell house from house."

Original post:
Study helps bring genome's 'dark matter' into light

Published: Sept. 18, 2013 at 2:44 PM

STATE COLLEGE, Pa., Sept. 18 (UPI) -- Two U.S. scientists said they discovered more on origin of genomic dark matter, non-coding RNA, which comprises more than 95 percent of the human genome.

B. Franklin Pugh, the Willaman chair in Molecular Biology at Penn State University, and Bryan Venters, who is on faculty at Vanderbilt University, discovered essentially all coding and non-coding RNA originates at the same types of locations along the human genome, Penn State said Wednesday in a release.

The scientists said their findings could help pinpoint exactly where complex-disease traits reside, since genetic origins of many diseases are outside of the coding region of the genome.

Pugh and Venters set out to identify the precise location of the beginnings of transcription, the first step in the expression of genes into proteins but they determined where proteins that initiate transcription of non-coding RNA were located along human chromosomes.

"So rather than look for the RNA product of transcription we looked for the 'initiation machine' that makes the RNA," Pugh said. "This 'machine' assembles RNA polymerase, which goes on to make RNA, which goes on to make a protein."

Pugh and Venters determined non-coding initiation machines recognized the same DNA sequences as the ones at coding genes, indicating they have a specific origin and their production is regulated, Pugh said.

"These non-coding RNAs have been called the 'dark matter' of the genome because, just like the dark matter of the universe, they are massive in terms of coverage ... . However, they are difficult to detect and no one knows exactly what they all are doing or why they are there," Pugh said. "Now at least we know that they are real, and not just 'noise' or 'junk.'"

Read the original here:
Scientists uncover milestone in genome's 'dark matter'