Transcription factor collaboration at the intersection of growth and patterning in the Hippo signaling pathway. Matthew Slattery¹, Roumen Voutev², Lijia Ma¹, Nicolas Negre¹, Kevin White¹, Richard Mann². 1) Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL; 2) Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY.

   The Hippo pathway has recently emerged as a key regulator of cellular proliferation. A downstream effector of the pathway, the transcriptional coactivator Yorkie (Yki), is an essential mediator of Hippo-regulated proliferation and is required for cell survival and proliferation in all imaginal discs. Yki lacks a DNA binding domain and must partner with sequence-specific DNA binding proteins in the nucleus to regulate gene expression. Two well-characterized Yki binding partners are the developmental regulators Scalloped (Sd) and Homothorax (Hth), which are required for cell survival and proliferation in the wing and eye, respectively. To better understand tissue specific gene regulation by these transcription factors at the downstream end of the Hippo pathway, we performed genome-wide chromatin immunoprecipiatation experiments for each factor in both the wing and eye-antenna imaginal discs. Strong, tissue-specific binding patterns are observed for Sd and Hth, while Yki binding is remarkably consistent across these two tissues. Importantly, binding events common to the eye and wing are also present for Sd and Hth; these general binding events are associated with genes regulating cell growth and proliferation, and can account for the vast majority of Yki binding. Tissue-specific binding events for Sd and Hth are consistent with developmental roles in the given tissue. These genome-wide binding data have also led to the identification of dozens of tissue-specific enhancers. Overall these results suggest that the transcription factors Sd and Hth use distinct binding strategies - one general and associated with Hippo signaling, the other tissue-specific and associated with developmental patterning - to regulate the distinct gene sets during development.