Methanococcus maripaludis is an ideal model organism for the study of transcriptional regulation in the Archaea. Through the study of a nitrogen assimilation regulon, novel aspects of transcriptional regulation are coming to light. A complete system has been identified for detailed study: a novel repressor protein NrpR, an inducer (2-oxoglutarate) that modulates NrpR activity, three regulated promoter regions, and three different nitrogen sources that result in different regulatory states. Each promoter region contains a different configuration of operator sites and has a different regulatory outcome. A robust set of genetic tools allows for testing the effects of various manipulations on regulatory outcome in vivo. The system provides the opportunity to understand in detail a particular system of transcriptional regulation in the Archaea. Experiments will determine the subunit structure of the NrpR-DNA complexes, the binding properties of NrpR to each promoter region, how 2-oxoglutarate modulates binding, and how regulatory outcome is determined. In addition genetic studies will be carried out to identify the domain of NrpR that binds 2- oxoglutarate and the domain that mediates multimer formation. Knowledge of regulation in the Archaea will be greatly increased. Comparison with known mechanisms in the Bacteria and Eukarya may reveal fundamental similarities or differences in regulatory mechanisms. Archaeal transcription is a good model for eukaryotic transcription due to its distinct relatedness but relative simplicity. These studies in Archaea have wide importance, as regulatory mechanisms are central to human development and disease.
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