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Chunk #18 — DISCUSSION

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Alcohol alters DNA methylation patterns and inhibits neural stem cell differentiation.
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Among the hypermethylated genes prevented by alcohol, Crabp1 is involved in retinol metabolism, and Wnt16 is involved in Wnt pathways. These genes are key to neural differentiation and neural patterning. Alcohol also affected programmed DNA methylation of a number of genes related to neural phenotype expression. Interestingly, many are related to transmitter receptors, sensory receptors, and an ion channel. The glutamate receptor AMPA (Gria3) and its interacting protein (Grip1), adrenergic receptor alpha 1a (Adra1a), cholinergic receptor muscarinic 1 (Chrm1), and potassium voltage-gated channel (Kcna1) are major receptors/channels key in neuronal transmission, communication, and signal transduction. In addition, of the 19 hypomethylated genes during differentiation prevented by alcohol, it is remarkable that > 50% them are sensory receptor genes specific to olfaction (Olr214, Olr304, Olr408, Olr611, Olr1646, Olr1139) and taste (Tas2r123, Tas2r7, T2r140, T2r18). It was remarkably, since the NSCs in this study are sensory in origin and may share common propensity, , that alcohol targeted the programmed DNA methylation of many sensory receptors. Our previous study in embryo development also revealed that the DNA methylation of a large number of