494A Poster - 06. Regulation of gene expression
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Christina Thomas; Ellen Armour ; Felice Elefant

Affiliation: Drexel University

Keywords:
j. epigenetics; d. ion channels

Experience-dependent (ED) plasticity is central for establishing memories and can influence the severity of AD progression. In this regard, we demonstrated that extracellular stimulation of rat hippocampal neurons in vitro triggers epigenetic gene regulator Tip60 nuclear import with concomitant genomic reorganization and synaptic gene induction. We further show that Tip60 nuclear import is recapitulated in the fly brain in vivo in response to stimulating neurons inducibly or by exposure to ED living conditions. Strikingly, Tip60 is found excluded from hippocampal nuclei in AD patients. Here we test the hypothesis that Tip60 extracellular mediated subcellular dynamics functionally impact synaptic gene control and cognition in vivo and that this process goes awry during early stages of AD. Using genetically modified Drosphila to inhibit the Shaker potassium pump within the neuronal membrane, we induced neuronal stimulation in the fly brain. We then used qPCR on RNA isolated from dissected brains in induced versus non-induced flies to assess expression levels of activity dependent plasticity genes we previously demonstrated to be bona-fide Tip60 targets. Strikingly, we found that as Tip60 increased within the nucleus, expression of specific Tip60 target neuroplasticity genes including dlg, dsh, and futsch were induced. These results suggest that Tip60 shuttles into the nucleus in vivo to activate gene expression of synaptic plasticity genes. Future directions will focus on exploring the colocalization of Tip60 with transcription factors (TFs) to further elucidate the mechanism underlying Tip60’s role in activity dependent gene control and ED plasticity.