• B.A. 1982, Lawrence University, Appleton, WI
  
• Ph.D. 1989, University of California, Berkeley
  
• Postdoctoral Researcher, 1990-92, University of Zurich, Switzerland 1993-96, UC San Diego.

David N. Arnosti

Research Interests

Transcriptional regulation in the context of development poses challenging and important questions. We utilize experimental and systems biology approaches to elucidate the mechanisms of transcriptional switches to understand developmental regulation in Drosophila and to gain an insight into general principles of eukaryotic gene regulation. Many aspects of development are crucially dependent upon transcriptional repression. In particular, short-range repression plays a critical role in regulation of complex patterns of Drosophila gene expression. Our work with Giant and Knirps repressors, as well as the CtBP and Rpd3 corepressors, has identified critical context-dependent features of target enhancers. We are developing molecular insights into the action of these proteins using transgenes and chromatin immunoprecipitation studies in embryos. These studies describe the biological context in which repressors are integrated, providing a deeper understanding of the molecular basis of development.

A popular model for transcriptional enhancers is the "enhanceosome" that features a highly constrained cis element design. Our analysis of short-range repressors on defined regulatory elements indicates that a second, more flexible form of design ("billboard" enhancer) better describes the activity of many developmental regulatory elements. Joining with the Systems Biology Initiative at MSU (www.egr.msu.edu/sysbio), we are applying mathematical approaches to decode the 'grammar' of cis regulatory elements, as revealed by our analysis of transcriptional repressors in Drosophila. This work will lead to the development of powerful bioinformatics approaches to interpret cis regulatory genomic sequences.

Retinoblastoma proteins are important regulators of the cell cycle in vertebrates, and Drosophila Rbf proteins perform similar roles. In collaboration with the Henry lab (MSU) we have identified novel cofactors of Rbf proteins, and are using biochemical and genetic analysis to understand the mechanisms of repression by these proteins in development.

Recent Publications