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Chunk #55 — Introduction — 5. Genome-Wide Approaches to Understand the Basis of Alcoholism

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The epigenetic landscape of alcoholism.
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Post-mortem brain studies have applied next generation sequencing approaches to detect changes in histone modifications underlying alcohol and cocaine use. Investigating human post-mortem brain from cocaine addicts and alcoholic patients, a parallel RNA-Sequencing (RNA-Seq) and ChIP-Sequencing(ChIP-Seq) experiment was performed in which RNA-Seq expression data was correlated with the H3K4me3 mark (Zhou, Yuan, Mash, & Goldman, 2011). The RNA-Seq data revealed 29 genes that regulate important neuronal functions showing coordinated regulation between cocaine and alcohol. For the ChIP-Seq data, around 250 H3K4me3 peaks were shared between the two treatments suggesting a shared epigenetic component between these two drugs of abuse (Zhou, Yuan, et al., 2011). A similar approach has been used in Drosophila to construct a gene network based on genome-wide histone H4 acetylation fold changes that occur at genomic loci following exposure to two drugs, benzyl alcohol and ethanol, utilizing the fact that these drugs produce mutual cross-tolerance. Among the 144 shared candidates discovered, the top gene clusters based on gene ontology belonged to the categories of transcriptional regulation, ion channels and synaptic plasticity genes (Ghezzi et al., 2013). Next-generation