Silencing “Selfish DNA” — Transposable elements (TEs) are mobile segments of genomic DNA that are often referred to as “selfish DNA” because they insert copies of themselves into different locations within the genome where they can cause harmful mutations. For this reason, it is important that cells repress TEs. A collaborative study between the laboratories of Drs. Arthur Skoultchi and Dmitry Fyodorov, published in the April 5 issue of Science, has revealed a novel mechanism for TE silencing that appears to protect chromosomes from injury. The current model highlights small RNA interference as the major pathway for TE repression; however, the Einstein team, including first author Dr. Xingwu Lu, discovered a new pathway, which silences TEs by compacting the regions of the genome in which they are located, effectively inactivating the selfish DNA. The researchers also show that the linker histone H1 specifically recruits a “code-writer” enzyme, Su(var)3-9, which marks the TEs for silencing. Dr. Skoultchi is professor and chair of cell biology, as well as the Judith and Burton P. Resnick Chair in Cell Biology; Dr. Fyodorov is associate professor and Dr. Lu is an associate in the same department.
Pompe’s Circumstance — Dr. Jeffrey Pessin has been awarded $2.5 million from the National Institute of Arthritis and Musculoskeletal and Skin Diseases to study the mechanism of Pompe’s disease. Resulting from deficiency in an enzyme that breaks down glycogen, a storage form of glucose in the liver and muscle that is the major source of energy for cells, Pompe’s disease can cause fatal heart and lung failure in infants. The process by which cells degrade damaged or unused components and molecules is called macroautophagy and late events in this pathway are damaged in this disease. The grant will aid Dr. Pessin’s research into the mechanism of muscle degradation in Pompe’s disease and how defects in macroautophagy contribute to this process. Ultimately, Dr. Pessin aims to design nutritional, exercise, and drug therapies that may help restore proper function in this pathway, which also might be used to treat related diseases. Dr. Pessin is professor of medicine and of molecular pharmacology, director of the Diabetes Research Center, and the Judy R. and Alfred A. Rosenberg Professorial Chair in Diabetes Research.
“Leuk”ing for a Cure — Dr. Ulrich G. Steidl had received an award of $1.8 million from The National Cancer Institute to study the role of a specific gene, HLX, in causing acute myeloid leukemia (AML), a cancer of white blood cells characterized by abnormal, rapid growth that interferes with the cells’ normal functions. The HLX gene encodes a protein that activates other genes (transcription factor); Dr. Steidl previously found that excessive amounts of HLX is associated with AML in both mouse models and in human patients. With this funding, he will study the mechanisms by which high amounts of HLX initiate AML; the genes that HLX targets for activation, which may work in concert to cause disease; and how HLX might be manipulated to identify possible therapeutic approaches. Dr. Steidl is assistant professor of cell biology and of medicine and is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research.