Medical Research

The George Washington University

Rong Li, Brett Shook, Yanfen Hu, Nu Zhang
Washington, D.C.
December 2020

Cellular memory refers to the ability of multiple cell types in animals and plants to “remember” a previous stress event and respond to future episodes with more rapid gene activation.  This self educating ability based on past experience endows organisms with enhanced survival and fitness under fluctuating and adverse environmental conditions.  How cells store records of past experience remains incompletely understood, but the current paradigm centers around chromatin-based epigenetic mechanisms.  A team from George Washington University and the University of Texas Health San Antonio, will test the hypothesis that paused RNA polymerase II (Pol II) at genes that are activated by a past stress signal can prime future gene activation, thus potentially endowing multiple cell types with enhanced responsiveness to repeated stress attacks.  The team’s model for cellular memory is a departure from the current chromatin-centered paradigm.  To establish proof-of-principle, the investigators will focus on two cell types with cellular memory: memory T cells and skin epithelial stem cells. Using mouse genetic models, they will interrogate the impact of Pol II pausing on the ability of these cells to preserve records of past experience of infection and injury.  Furthermore, the researchers will use cutting-edge genomic tools to survey the dynamics of Pol II movement and transcriptional activation in response to repeated rounds of external insults, with and without Pol II pausing.

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