1. Methyl-CpG-binding protein 2 mediates overlapping mechanisms across brain disorders.
- Author
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Bach S, Ryan NM, Guasoni P, Corvin AP, El-Nemr RA, Khan D, Sanfeliu A, and Tropea D
- Subjects
- Animals, Brain metabolism, Brain pathology, Brain Diseases pathology, DNA Methylation genetics, Disease Models, Animal, Gene Expression Profiling, Humans, Mice, Mutation genetics, Neurons metabolism, Neurons pathology, Rett Syndrome pathology, Brain Diseases genetics, Methyl-CpG-Binding Protein 2 genetics, Rett Syndrome genetics
- Abstract
MECP2 and its product, Methyl-CpG binding protein 2 (MeCP2), are mostly known for their association to Rett Syndrome (RTT), a rare neurodevelopmental disorder. Additional evidence suggests that MECP2 may underlie other neuropsychiatric and neurological conditions, and perhaps modulate common presentations and pathophysiology across disorders. To clarify the mechanisms of these interactions, we develop a method that uses the binding properties of MeCP2 to identify its targets, and in particular, the genes recognized by MeCP2 and associated to several neurological and neuropsychiatric disorders. Analysing mechanisms and pathways modulated by these genes, we find that they are involved in three main processes: neuronal transmission, immuno-reactivity, and development. Also, while the nervous system is the most relevant in the pathophysiology of the disorders, additional systems may contribute to MeCP2 action through its target genes. We tested our results with transcriptome analysis on Mecp2-null models and cells derived from a patient with RTT, confirming that the genes identified by our procedure are directly modulated by MeCP2. Thus, MeCP2 may modulate similar mechanisms in different pathologies, suggesting that treatments for one condition may be effective for related disorders.
- Published
- 2020
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