Biochemical Reconstruction of Epigenetic Transcriptional Memory

Type of Award: Catalyst
Date Awarded: September 2015
Award End Date: August 2017
Amount Awarded: $ 200,000.00
PI(s): Jason Brickner, PhD, NU; Alexander Ruthenburg, PhD, UChicago;

Abstract: Cells respond to environmental signals through changes in gene expression. Previous experience can profoundly alter a cell's response to environmental signals for multiple generations. Understanding the molecular basis of such adaptive mechanisms may reveal how the environment, aging and lifestyle can have a long-term impact on physiology. The Brickner laboratory has discovered a highly conserved, broadly utilized mechanism called epigenetic transcriptional memory that persists for generations, poising genes for more rapid expression. Using cell biological, genetic and molecular approaches, the Brickner lab has defined important aspects of this phenomenon. However, to fully understand transcriptional memory will require a new approach. Drawing on tools and expertise from the Ruthenburg laboratory, we propose to biochemically reconstitute transcriptional memory in a test tube. This new collaboration will serve as a powerful platform to identify new players in this process and to test mechanistic hypotheses about epigenetic inheritance.