Dr. Carey emphasizes that "The study provides a new direction to understand how histone and DNA methylation, two phenomena that play a significant role in stem cell differentiation and cancer, can communicate with each other to turn genes off. "

Although both histone and DNA methylation have long been recognized as hallmarks of euchromatic gene silencing, how these two processes cooperate to induce silencing has remained unresolved. In their upcoming paper, Dr. Carey and colleagues detail that mammalian HP1 proteins facilitate this cooperation.

They found that HP1 proteins, which bind to methylated histones, also interact with the DNA methyltransferase, DNMT1, to stimulate its DNA methylation activity. DNMT1, in turn, reinforced HP1 binding to methylated histones. Finally, the researchers showed that DNMT1-stimulated HP1 binding is required for gene silencing.

cshl

The new test assessed by Cheung and his colleagues is a way to hedge the bets.

The lead author of the paper is Hongjin Huang, PhD, associate director of liver diseases at Celera in Alameda, Calif. Huang and her Celera colleagues developed the test by initially scanning the DNA of more than 1,000 people who had hepatitis C. Out of 25,000 genetic variations tested, the researchers discovered seven that could be used together as a "signature" for predicting progression to cirrhosis in Caucasians.

The resulting gene signature - the Cirrhosis Risk Score - was then independently validated on 154 hepatitis C patients at Stanford, the University of Illinois-Chicago and California Pacific Medical Center. Among patients with early-stage liver disease, the researchers were able to divide them into a high-risk category based on their gene pattern, compared with those who had low-risk gene patterns. "The Cirrhosis Risk Score was superior to the known clinical factors, such as alcohol consumption, in predicting the risk of developing cirrhosis," said Cheung.

"This test allows both physicians and patients to make an intelligent decision about the urgency of beginning antiviral therapy," he said. "If a patient turns out to be low-risk, we might advise the patient to consider deferring treatment, avoiding unnecessary side effects and expense of current therapy."

Last June, Celera licensed Specialty Laboratories of Valencia, Calif., to perform the genetic test. The test currently costs about $500.