During FY13, we accomplished: 1) Initiated studies to knock-down key transcription factors in neuronal cell line SHSY5Y to study the effects on APP gene expression. Additional neuronal cell lines were screened to identify those with significant APP expression for future studies. We also evaluated the possibility of Jurkat cells, where siRNA -deepdendent down-regulation can be easily achieved, to study APP gene regulation. Additionally,E4BP4 was recently shown to regulate gene expression in T cells, suggesting that this cell line may be useful to study E4BP4-dependent APP expression. 2) Expressed zebrafish Forkhead proteins to study binding to computationally identified sites in the APP locus. Foxo down-regulation by siRNA in neuronal cell lines will follow binding studies.
|Shakes, Leighcraft A; Du, Hansen; Wolf, Hope M et al. (2012) Using BAC transgenesis in zebrafish to identify regulatory sequences of the amyloid precursor protein gene in humans. BMC Genomics 13:451|