The Influence of Alcohol Exposure on Alternative Splicing of the G9a Histone Methyltransferase

Abstract

Alternative splicing is a mechanism that leads to the generation of multiple mature mRNA products from a single gene. This process can produce isoforms, resulting in proteome diversity. In this study, we explore how EtOH exposure affects the alternative splicing of the G9a histone methyltransferase. G9a is an enzyme responsible for histone H3 lysine 9 dimethylation. The inclusion of G9a exon 10 is essential for neuron differentiation. The inclusion of the alternatively spliced exon 10 increases the nuclear localization of this histone methyltransferase and promotes a positive feedback loop that reinforces cellular commitment to differentiation. Studies in our laboratory have shown that EtOH exposure disturbs histone H3 lysine 9 dimethylation; therefore, this thesis describes the effect of EtOH exposure on alternative splicing on G9a histone methyltransferase. We examine the specific effects of EtOH exposure on inclusion or exclusion of exon 10 using a neural stem culture model. Here, cells were treated with 160, and 240 mg/dL EtOH for 72 hours, then allowed to recover for 4 days. We found that alcohol promoted the inclusion of exon 10, which may explain the increased levels of histone H3 lysine 9 dimethylation observed in alcohol-exposed cells.