Powell W, LaSalle JM

Scientific Notation:

Epigenetic regulation in the nervous system: Basic mechanisms and clinical impact. Edited by Nestler E, Sweatt D, Meaney M, Akbarian S. Elsevier Press, 267-279, 2013



Genomic imprinting is allele-specific silencing based on maternal or paternal inheritance via epigenetic mechanisms. All imprinted loci express a long non-coding RNA (lncRNA) in an allele-specific manner dependent on a differentially methylated region (DMR). We describe the general mechanisms of genomic imprinting during development, focusing on how lncRNA serve to translate the stable epigenetic mark of DNA methylation in order to allow for tissue specific patterns of imprinted gene expression. Disruption of an lncRNA encoded on chromosome 15q11-q13 plays a central role in the pathogenesis of the neurodevelopmental disorders Prader–Willi syndrome and Angelman syndrome, and regulation of gene expression throughout 15q11-q13 is important in brain development. We focus on 15q11-q13 as a model example for the role genomic imprinting plays in human brain development, and discuss the role other imprinted loci may play in brain development.

FPWR Grant:

R-loop formation and chromatin decondensation at the PWS critical locus