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Chunk #59 — Introduction — 6. Using Invertebrate Models to Study the Basis of Ethanol Phenotypes

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The epigenetic landscape of alcoholism.
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2006; Pietrzykowski et al., 2008). Epigenetic regulation of the BK channel gene promoter is complex and exhibits a spatio-temporal pattern of histone H4 acetylation following benzyl alcohol sedation in adult Drosophila brain. Acetylation increases become manifest at four hours after sedation and remain elevated 24 hours after sedation, however at different regions of the gene promoter. This presumably arises due to decreased acetylation at one region in the promoter being compensated by an increase in another region, which in turn may arise due to transcription factor activity or other cis- and/or trans- acting mechanisms (Wang, Krishnan, Ghezzi, Yin, & Atkinson, 2007). These data demonstrate the importance of genomic location in measuring histone modification changes as well as choosing the appropriate time-points. CREB signaling pathways in higher vertebrates regulate chromatin remodeling and mediate anxiety and ethanol-drinking behaviors (Moonat, Starkman, Sakharkar, & Pandey, 2010; Pandey, Ugale, et al., 2008) and have also been shown to affect ethanol tolerance in Drosophila (Wang, Ghezzi, et al., 2009). Drosophila CREB activates expression of the BK-type Ca2+ activated K channel gene (dslo) by binding to the promoter in response to benzyl alcohol sedation leading to a behavioral tolerance to the drug on a subsequent exposure (Wang,