Right after fertilization, embryos at the earliest stages of development tell their genes: "Forget what it was like in the sperm or egg where you came from." When the process of epigenetic reprogramming is defective in mouse development, the consequences in adulthood can include abnormal repetitive behaviors, scientists have shown. Their findings are published online on January 27, 2016 in the open-access journal eLife. The article is titled “Maternally Provided LSD1/KDM1A Enables the Maternal-to-Zygotic Transition and Prevents Defects That Manifest Postnatally.” “Our results demonstrate how defects in reprogramming may influence the development of altered behaviors, or even complex psychiatric disorders," says co-senior author David Katz, Ph.D., Assistant Professor of Cell Biology at Emory University School of Medicine in Georgia. After fertilization, the enzyme KDM1A (lysine specific demethylase 1A) appears to act as an epigenetic eraser, wiping away information carried on histones, the spool-like proteins that help package DNA. KDM1A removes histone methylation, a chemical modification that shapes the activity of nearby genes. Dr. Katz and graduate student Jadiel Wasson created genetically engineered mice that have KDM1A missing from their mouse oocytes (or egg cells), but present later in development. They teamed up with Todd Macfarlan, Ph.D., previously at the Salk Institute and now at the National Institute of Child Health and Human Development (NICHHD), to examine several mouse strains with alterations in the KDM1A gene. While these mice were created by genetic engineering techniques, Dr. Katz says they may simulate other disruptions of the reprogramming process after fertilization. Those disruptions might come from genetic changes or environmental influences on oocytes such as hormones or parental age, he says.
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