The University of Texas MD Anderson Cancer Center's Ronald DePinho and his colleagues report in Nature this week that homozygous deletions in redundant essential housekeeping genes could create possible targets for cancer therapeutics. The researchers write that ENO1 is a redundant housekeeping gene that is deleted in glioblastoma; ENO1 encodes part of endolase, which is a necessary part of glycolysis. ENO2, which is only expressed in neural tissues, also encode endolase. "Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells," the authors write, "and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes."
Also in Nature, Jacob Hanna from the Weizmann Institute of Science in Rehovot, Israel, and his colleagues write that the demethylase Utx regulates the induction of pluripotency in cells. They report that, in mice, Utx works with OSK reprogramming factors and uses its histone demethylase activity as part of iPSC formation. Further, the researchers note that depletion of Utx leads to changes in H3K27me3 demethylation activity, which then leads to changes in the repression of pluripotency promoting gene modules. "We identify Utx as a critical regulator acting at molecular switches during reprogramming to ground state pluripotency to safeguard an efficient, timely and authentic execution of H3K27 demethylation that is critical for this process," Hanna and his colleagues add.
Finally, Harvard Medical School's David Reich and colleagues report on their reconstruction of Native American population history using genotype information. They gathered data from 52 Native American and 17 Siberian groups that they genotyped at nearly 365,000 SNPs. From their analysis, they conclude that most Native American populations "derive their ancestry from a homogeneous 'First American' ancestral population, presumably the one that crossed the Bering Strait more than 15,000 years ago." They add, however, that they also noted evidence of additional gene flow from Asia, contradicting the idea that all present-day Native Americans came from that first wave. Eskimo-Aleut language speakers, Reich et al. found, inherited about half their ancestry from a second wave from Asia and the Na-Dene-speaking Chipewyan in Canada inherited about a tenth of their ancestry from a third wave. "We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America," the researchers write. "A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America."