Neurobiologia - Harvard Medical School, Massachusetts
Specializzazione in Neurobiologia
Disruption of DNA-‐methylation-‐dependent long gene repression in Rett syndrome
Harrison W. Gabel, Benyam Kinde, Hume Stroud, Caitlin S. Gilbert, David A. Harmin, Nathaniel R. Kastan, Mar#n Hemberg, Daniel H. Ebert & Michael E. Greenberg.
Here we identify a genome-‐wide length-‐dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes aMenuates RTT-‐associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutati0ons in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain.