The Mediator complex in gene regulation of the ß-globin locus: Analysis and characterization of Mediator subunit Med1/TRAP220 conditional knock-out mice

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The Mediator complex forms the bridge between transcriptional activators and the RNA polymerase II. Med1/TRAP220 is a key component of Mediator originally found to associate with nuclear hormone receptors. Med1 knockout mice die in embryonic development at day 11.5 days post coitum. So far, we could demonstrate that Med1 interacts physically with the erythroid master regulator GATA-1, is found at GATA-1 target genes and is required for GATA-1 dependent transcriptional activation. Thus, we concluded that Mediator subunit Med1 acts as a pivotal coactivator for GATA-1 in erythroid development (Stumpf et al., 2006). Now, we want to use conditional Med1 knock-out mice in order 1) to analyze the phenotype of Medl-deficient mice in adult erythropoiesis and 2) to dissect the molecular mechanism of transcriptional activation at the ßglobin locus, the best-studied gene locus for gene activation in higher eukaryotes. The overall goal of the proposed project is to understand the role of Mediator in gene activation.