genetic modifiers of mecp2 function in drosophila在果蝇遗传修饰符的mecp2函数.pdfVIP

Genetic Modifiers of MeCP2 Function in Drosophila 1 1 1 2,3 1,4,5 Holly N. Cukier , Alma M. Perez , Ann L. Collins , Zhaolan Zhou , Huda Y. Zoghbi , Juan Botas1,6* 1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America, 2 Neurobiology Program, Children’s Hospital Boston, Massachusetts, United States of America, 3 Departments of Neurology and Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America, 4 Departments of Neuroscience and Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America, 5 Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, United States of America, 6 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America Abstract The levels of methyl-CpG–binding protein 2 (MeCP2) are critical for normal post-natal development and function of the nervous system. Loss of function of MeCP2, a transcriptional regulator involved in chromatin remodeling, causes classic Rett syndrome (RTT) as well as other related conditions characterized by autism, learning disabilities, or mental retardation. Increased dosage of MeCP2 also leads to clinically similar neurological disorders and mental retardation. To identify molecular mechanisms capable of compensating for altered MeCP2 levels, we generated transgenic Drosophila overexpressing human MeCP2. We find that MeCP2 associates with chromatin and is phosphorylated at serine 423 in Drosophila, as is found in mammals. MeCP2 overexpression leads to anatomical (i.e., disorg