Understanding regulatory circuitry through large-scale genetic perturbation analyses

The long-term goal of the Frank Holstege’s group is to develop wiring-diagram models that describe how regulatory circuitry works at the molecular level across entire genomes. Their initial focus is on transcription regulation and their analyses require quantitative measurements of transcription rates for all genes, determination of transcription factor occupancy across the genome, mechanistical insight into signal transduction induced protein-modifications and their consequences for transcription, analysis of chromatin structure and modifications, the activity of co-regulatory protein complexes, etc. They have put together a powerful tool-box for genome-wide analyses that includes DNA microarray expression-profiling, genome-wide localisation analysis by ChIP on chip and various bioinformatics tools.