Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles.
Mei Zhong, Wei Niu, Zhi John Lu, Mihail Sarov, John I. Murray, Judith Janette, Debasish Raha, Karyn L. Sheaffer, Hugo Y. K. Lam, Elicia Preston, Cindie Slightham, LaDeana W. Hillier, Trisha Brock, Ashish Agarwal, Raymond Auerbach, Anthony A. Hyman, Mark Gerstein, Susan E. Mango, Stuart K. Kim, Robert H. Waterston, Valerie Reinke, Michael Snyder (2010). Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response, PLoS Genetics, 6(2): 1-13.