I propose to develop tools, datasets and methods for the genome-wide identification of genes regulated by transcription factors during the embryonic development of Caenorhabditis elegans. During the career development phase, I will use methods we have developed in the Waterston lab to generate an initial map of transcription factor activity with cellular resolution in the C. elegans embryo. In parallel I will develop technology to facilitate the efficient identification of downstream targets of transcription factors in the embryo. Once in my own lab, I will extend these methods to identify and characterize functional targets of many transcription factors on a genomic scale and to explore how transcription factors combine to regulate gene expression. The career development phase will be critical for this effort because of the need for development of methods, and because the transcription factor expression map I propose to produce will provide a critical integrating platform to use when choosing factors for genome-wide analysis and when interpreting the resulting data. Relevance to public health: Knowledge of how transcription factors act in development may provide information about how the same transcription factors function in cancers when inappropriately activated. Furthermore, human orthologs of genes identified in this study as regulated by developmentally important transcription factors may play roles in both normal development and disease.
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