Chromatin Regulation in Brain Development and Disease

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

In one research project, we are using molecular and genomic approaches to understand the function of these neuron-specific forms of DNA methylation. We are investigating why these modifications accumulate in neurons, what proteins associate with these modifications, how these modifications regulate transcription and genome integrity, and how mutations in regulators of DNA methylation lead to neurodevelopmental disorders and cancer. Another project is focused on a specific methyl-DNA-binding protein, MeCP2, mutations in which cause the neurodevelopmental disorder Rett syndrome. To investigate the function of MeCP2, we have developed an approach to rapidly degrade the MeCP2 protein in the mouse brain. We are using this approach to distinguish the immediate molecular consequences of acute MeCP2 loss from the secondary consequences of neurological impairment. These experiments will lend insight into the primary function of MeCP2, and this approach can be broadly applied to other proteins implicated in neurological disease.