SCIENCESCOPE DEVELOPMENT Anthros Happy: No Bones Gene-Suppressing Proteins Reveal About It Because $4 million buys a lot of anthropology Secrets of Stem Cells research, scientists are celebrating a grant of that size from the European Union to promote Scientists have taken a step toward unlocking teins. The vast majority of regulators primed research into human origins and anatomical the mystery of “stemness”: that is, decipher- to go into action later in development “are variation in primates. “It’s the largest ever in ing what makes embryonic stem (ES) cells being occupied and repressed by polycomb,” Europe for a project centered mostly on paleo- able to replicate indefinitely and retain the says Young. Many of these silenced regula- anthropology,” says Jean-Jacques Hublin of potential to turn into any kind of body cell. tory genes are also occupied by the the Max Planck Institute for Evolutionary According to papers in Cell and Nature this ES cell transcription factors Oct4, Sox2, Anthropology in Leipzig, Germany, a member week, key guardians of stemness and Nanog. Both sets of proteins of the European Virtual Anthropology Network. are molecules called polycomb “cooperate in keeping a cell group proteins. A team pluripotent and self-renewing,” The new consortium, launched last month from the Massachusetts says Jaenisch. at a meeting in Athens, Greece, will create Institute of Technol- “These papers are more than 30 doctoral and postdoctoral posi- ogy (MIT) and the really exciting because tions at 15 participating institutions. The young Whitehead Institute they point the way to scientists will learn the latest techniques in for Biomedical Re- one of the next levels 3D imaging, computer modeling, and virtual search in Cambridge, of stem cell research,” reconstructions of humans, apes, and their Massachusetts, says Princeton Uni- ancestors (Science, 3 June 2005, p. 1404). reports that these versity stem cell scien- –MICHAEL BALTER proteins act in con- tist Ihor Lemischka. cert with others to The new, fuller pic- Super-K A-OK repress most of the ture of polycomb group Japan’s Super-Kamiokande neutrino detector regulator genes whose proteins, adds Young, is back at full strength, 4.5 years after a shock proteins turn on key dev- may help scientists guide wave triggered by the implosion of a damaged elopmental genes. This ES cell gene expression photomultiplier tube destroyed 7000 of its keeps the ES cell in an and push cell popu- 11,000 sensors (Science, 23 November 2001, undifferentiated state. lations to develop Who regulates the regulators? A polycomb p. 1630). Super-Kamiokande made headlines Polycomb group protein silences hundreds of genes that will direct into desired types, in 1998 by providing evidence that neutrinos proteins are known to the differentiation and development of ES cells such as neurons or play a vital gene- when activated. insulin-making pan- have mass, but manufacturing replacement suppressing role in the creatic cells. photomultiplier tubes after the subsequent development of organisms as diverse as fruit The same issue of Cell also features a accident took a while. “There is still a lot of flies and humans (Science, 29 April 2005, report from the laboratory of Eric Lander at neutrino research to be done,” says Kamioka p. 624). Now, the researchers have tracked the Broad Institute of Harvard and MIT that Observatory Director Yoichiro Suzuki. this role back to the very earliest stage of devel- highlights the importance of chromatin, the –DENNIS NORMILE opment. These proteins are “the founding protein package surrounding DNA, in keep- ingredient for development,” says Rudolf ing mouse ES cells pluripotent. The scientists, Postdocs off the Docket Jaenisch, an author of both studies. “This is a led by Bradley E. Bernstein, found certain Two former postdocs at Harvard Medical major step forward in efforts to map the regula- chromatin motifs near genes important for School in Boston last week admitted that they tory circuitry of embryonic stem cells, which development that can repress the genes while took research material from their lab without constitutes the founding circuitry of human at the same time keeping them poised for acti- permission, but charges against them were beings,” adds co-author Richard Young. vation. These chromatin features, which they dropped as part of a deal with prosecutors. In the Cell study, the researchers surveyed labeled “bivalent domains,” exert control over The saga began in early 2000, when Jiang all 3 billion base pairs in the human genome many of the same regulatory genes targeted Yu Zhu and his wife Kayoko Kimbara shipped and identified every gene that a polycomb by polycomb proteins. reagents from Harvard to the University of group protein, Suz12, binds to in ES cells. The three papers “provide a wealth of Texas, San Antonio, where Zhu had been offered They started by treating ES cells so that detailed information” on what keeps ES cells employment (Science, 28 June 2002, p. 2310). Suz12 remained bound to its DNA targets pluripotent, says Vincenzo Pirrotta, a Researchers often transfer such materials when even after the cells were broken open. They molecular biologist at Rutgers University in they change jobs, but the couple failed to seek then dumped the cells’ contents onto a chip Piscataway, New Jersey. The polycomb permission from their professor, sparking a containing DNA representing all of the papers demonstrate that those proteins and court case. Prosecutors initially alleged that the human genome. The DNA sequences affixed ES cell transcription factors bind to “a largely couple intended to use the reagents, used in to Suz12, which were labeled with a dye, common set of genes.” The Bernstein paper , 1-13 (2006) organ-transplant research, to produce a com- bound to complementary sequences on the then addresses how genes silenced by these 125 chip, revealing their identity. The scientists factors ultimately become activated. Toge- mercial product. After a 2002 arrest, the pair also report in Nature on a similar study with ther, says Pirrotta, the papers have “defined pleaded not guilty. Under a deal with the gov- mouse ES cells using Suz12 and three other the important players and the sites of action” ernment, the indictment will be dismissed in ET AL., CELL polycomb group proteins. that must be studied to get to the root of what 1 year if the pair stays out of trouble. The two efforts identified hundreds of it is to be a stem cell. –ANDREW LAWLER

CREDIT: LEE CREDIT: genes targeted by the polycomb group pro- –CONSTANCE HOLDEN

www.sciencemag.org SCIENCE VOL 312 21 APRIL 2006 349 Published by AAAS