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Chunk #57 — Discussion

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Decitabine alters the expression of Mecp2 isoforms via dynamic DNA methylation at the Mecp2 regulatory elements in neural stem cells.
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Our results on the ability of 2.5 μM decitabine to upregulate Mecp2e1 (but not Mecp2e2) suggest that the two isoforms may have different sensitivities to drugs/chemicals. This observation is in agreement with the previous report on the higher sensitivity of Mecp2e1 than Mecp2e2 to Bisphenol A [69]. These observations further suggest that the differential sensitivity to drugs might be used to specifically induce only one Mecp2 isoform. This is also important because overexpression of Mecp2e2, but not Mecp2e1 causes neuronal cell death [10]. Hence, our study provides a functional relevance of DNA demethylation at the Mecp2 REs by decitabine causing upregulation of Mecp2e1, but not Mecp2e2.