Sometime between the age of 6 and 18 months, after a period of seemingly normal development, girls affected with Rett Syndrome lose interest in play; they gradually become withdrawn and anxious, develop autistic-like behaviors, and acquire specific symptoms like repetitive teeth-grinding and hand-wringing. This devastating neurological disease affects one in 15,000 female children. Just five years ago, Rett Syndrome was tracked to mutations in a gene on the X chromosome, MECP2 . But how this gene, not previously associated with the brain or nervous system, could cause a neurological developmental disorder remained a puzzle. Now, a team of scientists with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory has developed new methods and overturned mistaken assumptions to discover how the product of this gene, the protein MeCP2, can remodel chromatin, the material that makes up chromosomes. For the first time a human disease — Rett Syndrome, the first identified epigenetic disease — has been linked to specific defects in the three-dimensional folding of chromatin. The research was supervised by Terumi Kohwi-Shigematsu, a biochemist with Berkeley Lab’s Life Sciences Division; it reveals how mutated MeCP2 protein represses genes, and identifies some of the most important of those genes. Kohwi-Shigematsu and her colleagues, Shin-ichi Horike, Shutao Cai, Masaru Miyano, and Jan-Fang Chen, report their results in advanced online publication of the January issue of Nature Genetics.
