Quantifying quadruplexes
The paper:
J.L. Huppert and S. Balasubramanian, "G-quadruplexes in promoters throughout the human genome," Nucleic Acids Res, 35:406–13. (Cited in 56 papers)
The finding:
University of Cambridge computational biologists Julian Huppert and Shankar Balasubramanian scanned the human genome in search of the telltale sequences of guanine-rich, four-stranded structures that regulate gene transcription, called G-quadruplexes. The researchers uncovered G-quadruplexes in about 40% of promoter regions across the genome, with most clustered near transcription start sites.
The impact:
Many important promoters—including ones for cancer genes and vascular growth factors—were known to contain G-quadruplexes, but no one had a clue as to whether they performed a specific function. "So it was very important to demonstrate that this wasn't a fluke," says Laurence Hurley, a medicinal chemist at the University of Arizona in Tucson.
The follow-ups:
Huppert's team found that G-quadruplexes also pop up...
The application:
Hurley started a biotech company called Cylene, which is conducting Phase II trials on a small molecule to target the G-quadruplex in the cancer-promoting gene c-myc.
Location | G-quadruplex density compared to genome average |
Promoter region | 230-fold increase |
1 kb upstream of promoter | 6.1-fold increase |