An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

Short-term external stimuli can induce long-term changes in gene expression patterns in organisms, which under particular instances are even transmitted through generations. We are testing the role of the stress-induced chaperone Hsp90 in controlling long-term decisions sustained by PcG/TrxG regulators. By mapping chromatin-binding sites of this chaperone at high resolution across the Drosophila genome using ChIP-seq, we find that Hsp90 localizes at promoters of many PcG/TrxG-controlled genes. Computational and biochemical analyses indicate that Hsp90 regulates target genes by affecting RNA polymerase II (pol II) pausing, via stabilizing the Negative Elongation Factor complex. Hsp90 is required for optimal activation of paused genes in Drosophila and mammalian cells in response to environmental stimuli such as bacterial endotoxins and heat-shock. The goal of this project is to establish regulatory networks, connecting stress sensing and long-term cellular memory.

Participants in the project:

• Dr. Ritwick Sawarkar (postdoctoral fellow; molecular and cellular biology)
• Cem Sievers (graduate student; computational biology)