Transcription Factor Network Dynamics in Development. Ilaria Rebay, Jean Francois Boisclair Lachance, Matthew Hope, Aaron Mitchell-Dick, James Porter, Jemma Webber. Ben May Dept, Univ Chicago, Chicago, IL.

   Precise spatial and temporal control of gene expression is fundamental to all biological processes. For example, even minor imbalances in gene regulatory networks can compromise the robustness and accuracy of developmental programs. A broad goal of my lab's research is to understand the dynamical properties of transcription factor networks that enable them to integrate instructions from multiple signaling pathways and to direct appropriate cell fate transitions during development. One of the projects currently underway seeks to understand the function and regulation of the Yan network, a transcriptional effector circuit that operates downstream of receptor tyrosine kinase signaling. At the core of the network are two antagonistic ETS-domain transcription factors, the repressor Yan and the activator Pointed. A regulatory web of feedback loops and interactions confers switch-like behavior to the system. Thus in response to pathway activation, attenuation of Yan-mediated repression and stimulation of Pointed-mediated transcription of common target genes triggers differentiation programs previously blocked by Yan. We are using an integrative combination of molecular genetic, genomic, biochemical and computational analysis of Yan network components and behaviors to explore how the interplay between cis-regulatory architecture, protein-protein interactions, and three-dimensional chromatin organization ensures accurate and robust output from this system. Our latest findings and models will be presented.