495B Poster - 06. Regulation of gene expression
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Ellen Armour; Gabrielle Greco; Felicity Khoa; Felice Elefant

Affiliation: Drexel University

Keywords:
j. epigenetics; f. learning/memory

Experience-dependent (ED) plasticity is central for establishing memories and is driven by epigenetic mechanisms that regulate dynamic gene transcription in response to neuronal stimulation. Our lab has previously shown the histone acetyltransferase (HAT) Tip60 shuttles into the nucleus in vitro to regulate activity dependent gene control of synaptic plasticity genes. Furthermore, we also found that Tip60 is largely excluded from the nucleus in hippocampal neurons from Alzheimer’s disease (AD) patients. However, if and how Tip60 shuttles in the in vivo brain to regulate the expression of activity dependent synaptic genes is yet to be elucidated. Here, we used immunohistochemistry (IHC) to compare the subcellular localization of Tip60 HAT in the Drosophila brain under normal conditions and in response to stimulation of fly brain neurons in vivo either by inducibly activating potassium channels using genetic manipulation or by exposure to natural ED living conditions. Strikingly, we found that both inducible and ED living condition mediated neural induction triggered changes in Tip60 subcellular localization evidenced by a significant increase of Tip60 in the nucleus with concomitant induction of previously identified Tip60 target genes. Our results support a model by which neuronal stimulation promotes nuclear import of Tip60 to promote induction of activity-dependent neuroplasticity gene transcription. Future work will focus on labeling Tip60 with a GFP tag to track its in vivo nucleocytoplasmic transport in real-time and determine whether this processes is disrupted in brains from Drosophila that model AD. We will also mutate the nuclear localization sequences and nuclear export sequences to determine the functional impact of disrupting Tip60 nucleocytoplasmic transport on cognition and use chromatin assays to explore underlying mechanisms.