We have recently discovered the activity-dependent, intracellular O-GlcNAcylation of MeCP2 in embryonic cortical neurons. This research proposal aims to 1) identify which amino acids of MeCP2 are O- GlcNAcylated and 2) determine the functional significance of O-GlcNAc-MeCP2. We hypothesize that following seizure, MeCP2 O-GlcNAcylation triggers the dissociation of MeCP2 from certain gene promoters it is involved in repressing, thereby triggering the expression of those genes. This finding will further the understanding of the molecular mechanisms governing Rett syndrome, a common form of female mental retardation that is characterized by postnatal onset and seizures, and caused by loss of MeCP2 function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS056525-04
Application #
7675935
Study Section
Special Emphasis Panel (ZRG1-GGG-G (29))
Program Officer
Mamounas, Laura
Project Start
2006-09-01
Project End
2010-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$3,954
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Clark, Peter M; Rexach, Jessica E; Hsieh-Wilson, Linda C (2013) Visualization of O-GlcNAc glycosylation stoichiometry and dynamics using resolvable poly(ethylene glycol) mass tags. Curr Protoc Chem Biol 5:281-302
Rexach, Jessica E; Clark, Peter M; Mason, Daniel E et al. (2012) Dynamic O-GlcNAc modification regulates CREB-mediated gene expression and memory formation. Nat Chem Biol 8:253-61
Rexach, Jessica E; Rogers, Claude J; Yu, Seok-Ho et al. (2010) Quantification of O-glycosylation stoichiometry and dynamics using resolvable mass tags. Nat Chem Biol 6:645-51
Rexach, Jessica E; Clark, Peter M; Hsieh-Wilson, Linda C (2008) Chemical approaches to understanding O-GlcNAc glycosylation in the brain. Nat Chem Biol 4:97-106