Epigenetic Mechanisms in Rett Syndrome
Janine M. LaSalle
from: Epigenetics: Current Research and Emerging Trends (Edited by: Brian P. Chadwick). Caister Academic Press, U.K. (2015) Pages: 199-216.
Abstract
Mutations in the X-linked gene MECP2 cause the neurodevelopmental disorder, Rett syndrome, an epigenetic disease at two levels. First, MECP2 is subject to X chromosome inactivation and MECP2 heterozygous female Rett patients are mosaics of both mutant and wild-type expressing cells. Differences in X chromosome inactivation patterns can therefore affect the phenotypic severity and pathogenesis of Rett syndrome and related disorders of MECP2 mutation or duplications in females. Second, MECP2 encodes methyl CpG binding protein 2, a member of the methyl binding domain (MBD) family of epigenetic readers of DNA methylation marks in chromatin. MeCP2 is an inherently disordered protein composed of different isoforms, post-translational modifications, and cofactor associations that dynamically change and mediate a variety of different functions in both neurons and non-neuronal tissues. Investigating both of these levels of epigenetic complexity of MECP2 is likely to be critical in understanding the molecular pathogenesis and disease progression, as well as developing effective therapies for Rett syndrome read more ...
