Science Concentrates EPIGENETICS
New epigenetic mark for mammals
Sampling of remote U.S. lakes like Lonesome Lake, Wyoming, showed rising phosphorus.
Adenine, a DNA base other than cytosine, also gets methylated
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C&EN | CEN.ACS.ORG | APRIL 4, 2016
WATER
EPA uncovers mysterious phosphorus pollution Unknown processes dump phosphorus into remote lakes and streams An unknown process is dumping phosphorus into streams and lakes across the U.S., according to a new study (Environ. Sci. Technol. 2016, DOI: 10.1021/acs.est.5b05950). The resulting increase in phosphorus in these water bodies could lead to toxic algal blooms and degraded habitat for fish, birds, and frogs. High phosphorus levels in streams and lakes typically result from sewage discharge and agricultural runoff. But the new work finds phosphorus pollution in remote areas far from such sources, leaving researchers scratching their heads about where it came from. EPA stumbled on these results while analyzing data collected as the agency tracked the health of the nation’s waters, says EPA biogeochemist John L. Stoddard. Every five years, the agency measures the concentration of important ions and nutrients in a selection of lakes and streams. Phosphorus was the only measured nutrient that changed, Stoddard says. Across the country, median total phosphorus in streams more than doubled from 26 to 56 µg/L over the past 10 years. In lakes, levels rose from 20 µg/L in 2007 to 37 µg/L in 2012. “The change was most dramatic in the more pristine parts of the country,” he says. To avoid significant changes to ecosystems, phosphorus concentrations must stay below 10 µg/L. By 2014, only 1.6% of stretches of streams tested fell below that level. “This is a surprising and provocative result that we wouldn’t have seen if EPA hadn’t been doing routine monitoring,” says Emily H. Stanley, an aquatic biogeochemist at the University of Wisconsin, Madison. Stanley and the EPA scientists have some ideas about the sources of the extra phosphorus. Big storms, which have increased in the past 20 years, can wash soil particles rich in phosphorus into streams and lakes. But perhaps the most likely cause is atmospheric deposition from sources such as dust. “Phosphorus sticks to soil and clay particles in dust and gets blown around by wind,” Stanley says. The increases in big storms and dust are linked to climate change, Stoddard says, so it will be difficult to stop the trend.—JANET PELLEY, special to C&EN
JANICE BRAHNEY
Cytosine bases here and there in DNA are famously decorated with methyl groups, chemical modifications that silence genes so that specific cells express only certain, appropriate DNA sequences. This safety strategy ensures, for instance, that eyelash cells don’t sprout from spleen cells. Thanks to new research, cytosines can no longer claim to be the only bases that slip on a methyl group in mammals. Adenine bases can also be methylated, says Yale University’s Andrew Z. Xiao, whose research team found the modification in mouse stem cells. Xiao and his team recently identified an enzyme responsible for removing the chemical mark from adenine (Nature 2016, DOI: 10.1038/nature17640). Although adenine methylation has long been observed in single-celled organisms, researchers didn’t think it decorated the DNA of multicellular organisms, comments Gerd P. Pfeifer, who studies epigenetics at the Van Andel Research Institute in Grand Rapids, Mich. “Adenine methylation in DNA was totally ignored for a very long time,” Pfeifer says. By 2015, the epigenetic mark had been reported in algae, plants, mosquitoes, fruit flies, and worms—discoveries in multicellular organisms that tantalized researchers with the possibility that mammalian DNA may also CH3 possess the mark. Last December, researchHN ers at the University of Cambridge reported N initial evidence suggesting the epigenetic N mark was also found in adult human and N N mouse cells (Nature Struct. Mol. Biol. 2015, DOI: 10.1038/nsmb.3145). Methylated Methylated adenine appears to be quite adenine rare in mammalian cells, Xiao says. For example, DNA in mouse stem cells has about six to seven methylations per million adenine bases, a frequency several orders of magnitude rarer than cystosine methylation. To find the mark in mouse stem cells, Xiao’s team carefully measured the kinetics of polymerase enzymes as they replicated DNA during sequencing. The rate of the replication slowed when the enzymes hit a methylated adenine. The team then used mass spectrometry to confirm the presence of the mark at these spots on the DNA. In the new study, Xiao and colleagues also took a stab at figuring out what role the epigenetic mark plays. They found that, like methylated cytosines, methylated adenines silence genes in mouse stem cells, albeit using an entirely independent system of enzymes. Curiously, research in worms and flies suggests adenine methylation is involved in activating nearby genes, a function opposite to what Xiao’s group found in mouse stem cells. “I’ve spent a lot of time trying to figure out this difference,” he says. “We need to do a lot more research before we can connect all the dots.”—SARAH EVERTS
