Project 1. Epigenetics in Human Disease; Molecular Mechanisms of Rett syndrome
Perhaps the best example to study the role of epigenetics in human disease is Rett syndrome (RTT). RTT is a progressive neurological disorder and a leading cause of mental retardation in females (1:10,000). RTT is mainly due to de novo mutations in methyl-CpG binding protein-2 (MECP2) gene. MeCP2 is an epigenetic regulator that binds to methyl CpG (5mC and 5hmC) at its target genes and controls their expression. Two MeCP2 isoforms (E1 and E2) exist with redundant and non-redundant properties. To clearly understand MeCP2 involvement in brain disorders for potential therapeutic strategies, we study the molecular functions of MeCP2 isoforms in brain stem cells, and different cell types of brain. We study how Mecp2/MECP2/MeCP2 isoforms are controlled by epigenetic mechanisms. Our results are expected to have significant impact for designing novel therapeutic strategies for children suffering from RTT.