Signals and transcription: a view from the binding site, with thoughts on the informatics of patterning

23 Mar 2012

Scott Barolo
Department of Cell and Developmental Biology
University of Michigan Medical School

Abstract

A handful of ancient cell-cell signaling pathways, whose function is purely informational, are major determinants of developmental pattern, organogenesis, stem cell fates, and cancer (which can be considered a disease of misinformation). These signal transduction pathways, including Hedgehog, Wnt, Notch, and RTK/Ras/MAPK, act primarily by regulating specific transcription factors (TFs), which bind to specific DNA sequences within enhancers of pathway target genes and control their expression.

Our lab tries to understand the cell's response to signaling by dissecting and decoding the cis-regulatory DNA of signal-regulated enhancers. In this chalk talk, several questions will be addressed (but probably not answered):

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