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This Week in PNAS: Dec 8, 2010

In this week's PNAS Early Edition, researchers at the Sanford-Burnham Medical Research Institute, along with their collaborators at Columbia University, show that deletion of DDB1 "abrogates the self-renewing capacity of hepatocytes, resulting in compensatory proliferation of DDB1-expressing hepatocytes." In addition, the team shows that "constitutive stimulation of this regeneration process leads to development of hepatocellular carcinoma, which surprisingly contains no disruption of the DDB1 gene." The authors suggest this indicates a "cell-non-autonomous role of DDB1 inactivation in tumor initiation." In this way, the researchers suggest, viruses and hepatoxins may promote liver tumors by "driving hepatocyte turnover" rather than by targeting cancer cells directly.

A public-private research collaboration of investigators at Massachusetts General Hospital and the Woburn, Mass.-based Exiqon Corporation suggests that locked nucleic acids are useful tools for interrogating regulatory RNAs and "offer a window of opportunity to target epigenetic modifications." The team targeted LNAs at Xist RNA and found its transcript stability unaffected. "By targeting different Xist regions, we identify a localization domain and show that polycomb repressive complex 2 is displaced together with Xist," the authors write. When that data was coupled with time-course analysis of RNA re-localization, they also showed that "Xist and PRC2 bind to different regions of the X at the same time, but do not reach saturating levels immediately."

A trio of researchers at the University of California, Berkeley, describes the epigenetic regulation of the maize transposon MuDR and its association with vegetative phase change. "Given the great danger that transposon activity represents to the germ line," the authors write, shifts in epigenetic regulation during the plant's transition from juvenile to adult growth may be of functional importance.

In another paper published online in advance in PNAS, investigators at Johns Hopkins University School of Medicine and Stevenson University in Maryland show that the transposon "Hermes inserts into DNA in nucleosome-free regions in vivo." More specifically, the team sequenced de novo Hermes insertion sites within the Saccharomyces cerevisiae genome "to better characterize intrinsic sequence specificity" and "to characterize the effect of intracellular factors such as chromatin on target site selection." The team shows that Hermes targeting is "profoundly affected by chromatin structure," in that "the subset of genome-wide target sites used in vivo is strongly associated with nucleosome-free chromatin."

The Scan

Could Cost Billions

NBC News reports that the new Alzheimer's disease drug from Biogen could cost Medicare in the US billions of dollars.

Not Quite Sent

The Biden Administration likely won't meet its goal of sending 80 million SARS-CoV-2 vaccine doses abroad by the end of the month, according to the Washington Post.

DTC Regulation Proposals

A new report calls on UK policymakers to review direct-to-consumer genetic testing regulations, the Independent reports.

PNAS Papers on Mosquito MicroRNAs, Acute Kidney Injury, Trichothiodystrophy

In PNAS this week: microRNAs involved in Aedes aegypti reproduction, proximal tubule cell response to kidney injury, and more.