Information, Enhancers, and Cell Signaling: a View from the Binding Site. Scott Barolo. University of Michigan Medical School, Ann Arbor, MI.

   Cell-cell signaling pathways such as Hedgehog, RTK/MAPK, Notch, BMP, and Wnt relay extracellular patterning information to transcription factors (TFs), which determine developmental cell fates by controlling gene expression. Signal-regulated TFs bind to specific DNA sequences within enhancers of pathway target genes. Enhancers then integrate these signaling inputs with other types of information to precisely control gene expression in response to signaling.

   Our lab tries to understand the cell's responses to these signals by dissecting and decoding the cis-regulatory DNA of signal-regulated enhancers. Because these pathways are extremely pleiotropic that is, they are active in many different cell and tissue types during development and adult life we are particularly interested in how cis-regulatory DNA sequences are able to interpret these "generic" signals in a context-specific manner. Simple combinatorial logic is part of the answer to this question, but upon close examination, it's clear that this is far from the whole story. In this talk, several questions will be addressed (but probably not answered):

   1. Where is the complexity in animal genomes? (Hint: it's not in the number of genes or transcripts.)
   2. What is the information content of a single TF binding site? Of a pair of sites? Of an enhancer?
   3. Do different types of TFs carry different amounts, or distinct types, of patterning information?
   4. Do enhancers really "integrate" patterning information from multiple TFs, and if so, how does this computation physically occur?