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Roles of Methyl-CpG Binding Protein 2 in Immune Function

Cronk, James
Thesis/Dissertation; Online
Cronk, James
Kipnis, Jonathan
Methyl-CpG binding protein 2 (MeCP2) was one of the first methyl-CpG binding proteins identified. Since its discovery, MeCP2 has been shown to be an essential regulator of gene transcription via its role in orchestrating transcriptional complexes associated with methylated CpG islands in the genome. In 1999, mutations in MeCP2 were identified as the primary cause of Rett syndrome. Several years later, another MeCP2-related neurodevelopmental disorder was identified, called MeCP2 duplication syndrome. Due to the clear association of both disorders with neurologic pathology, and the high levels of MeCP2 expressed by neurons, it was largely assumed that the complete etiology of disease in both disorders was explained by defects in neuronal function. However, it has since become clear that many cells throughout all tissues express and require MeCP2 for their normal function. Thus, understanding both the basic biology and disease relevance of MeCP2 in non-neuronal cell types has become an important question. This is particularly true for the immune system, where nearly every cell expresses MeCP2. Presented here is evidence for the importance of MeCP2 in function of the immune system; 1) MeCP2 regulates microglia and macrophage gene expression in response to multiple stimuli, and 2) overexpression of MeCP2 leads to a dysfunctional immune response and mortality upon influenza A infection. Together, these results demonstrate that MeCP2 is an important regulator of immunity in multiple contexts, and thus immune roles for MeCP2 should be considered as a fundamental aspect of MeCP2 function.
University of Virginia, Department of Neuroscience, PHD (Doctor of Philosophy), 2016
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PHD (Doctor of Philosophy)
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