Charakterisierung der Bedeutung von Sp-Transkriptoren in neuronen-spezifischen Genexpression

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The cell type specific control of gene expression is critical for brain development and function. Many neuron-specific promoters contain GC box elements, which are important for expression of numerous genes in neurons. The sequence specific transcriptional control via GC boxes is largely determined by Sp transcription factors. They have been implicated in the regulation of many different genes involved in diseases like cancer and neurodegenerative diseases, nevertheless the regulation and activity in neurons is poorly understood. This project will focus on the role of Sp transcription factors in neuron specific gene expression. As a model we will investigate the expression of the cyclin dependent kinase 5 activator p35. Previous work by the Gill lab has shown that the p35 promoter contains a repeated GC box element that is necessary and sufficient for neuron specific expression and is bound by Sp proteins in vitro. We will characterize the interaction of individual Sp transcription factors with the p35 promoter in vivo and their effect on neuronal differentiation. Furthermore, we intend to identify new neuronal target genes of Sp4, which in contrast to Spl and Sp3, is expressed predominantly in the developing nervous system. We hypothesize that Sp4 plays an important role in differentiation and function of neurons through binding and activation of p35promoter and other neuron-specific genes containing GC box elements in their promoters.