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Chunk #24 — IDENTIFICATION OF TRANSCRIPTION FACTORS CO-REGULATING THE EXPRESSION OF PREDISPOSING GENES

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Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the Brain.
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The specific molecular mechanisms through which ethanol regulates gene expression have been elucidated for a small number of genes [72]. In particular, a consensus sequence named alcohol response element (ARE) was identified in the second exon of the gene encoding the α4 subunit of the GABAA receptor (Gabra4) and proved to be essential for up-regulation of Gabra4 expression by ethanol in cortical neurons [73]. Further analysis revealed that the ARE sequence is a binding site for the transcription factor heat shock factor 1 (Hsf1) and that ethanol induces the nuclear translocation of Hsf1. Hsf1 was also shown to mediate the up-regulation of synaptotagmin 1 (Syt1) expression by ethanol, and ethanol induction of a subset of genes encoding synaptic vesicle fusion proteins correlated with the presence of multiple ARE sequences in promoter and intronic regions [74]. Interestingly, a highly homologous sequence, coined ethanol and stress response element (ESRE), was identified in the promoter region of several genes acutely induced by ethanol in the nematode, including several members of the heat shock protein family [16]. Accordingly, molecular chaperones were also differentially expressed