Grant: Operating Grant

Rett syndrome is a slow progressing neurodevelopmental disease,that affects approximately 1 in 10,000 infant females. 85% of the clinical cases have been traced to mutations of MeCP2, a vital regulatory protein that cannot function properly when mutated, leading to severe language and learning disabilities. MeCP2 binds specifically to methylated DNA sequences and these complex interactions are modulated by the state of chromatin. Chromatin consists of a DNA wrapped around proteins known as histones, and is prevalent in the cells of higher organisms (i.e., plants and animals including humans). The functions and interactions of MeCP2 with chromatin are not well understood. Recently, our lab has provided well-supported evidence that MeCP2 is abundant in the brain, prefers binding to specific chromatin sequences, and is highly enriched in certain chromatin regions. In this proposed study, we plan to further investigate the MeCP2-chromatin interactions by characterizing MeCP2 containing chromatin structures and determining specific MeCP2 interaction sites with histones. Results of this study will assist us to better understand the functions of MeCP2 in the context of chromatin, to develop strategies and interventions to possibly reverse the impairments associated with Rett syndrome.