Spatial feedback between epigenetic regulation and chromatin organization

A central challenge in the genome-organization field is to understand how a highly heterogeneous and dynamic range of chromatin conformations can nevertheless produce precise and robust spatiotemporal gene-expression programs. Closely linked to this question is whether the same underlying mechanisms can encode both epigenetic memory and gene-expression plasticity.

The spatial feedback model introduced in Murphy & Boettiger, Nat. Genetics, 2024 offers an appealing explanation. Building on the observation that diverse chromatin conformations and varying levels of condensation can still maintain a functionally repressed genetic state, the model proposes that dynamic long-range chromatin interactions reinforce existing gene repression, whereas their absence allows for the plasticity needed to adopt a new expression state. In other words, epigenetic regulators (like HP1 and Polycomb) can alter the biophysical properties of chromatin to promote memory of gene repression. Thus, the role of chromatin organization in gene repression is to stabilize the “off” state rather than physically exclude activators.

This concept of spatial feedback extends beyond heterochromatin and epigenetic memory. I anticipate that it will provide a broader framework for understanding how statistical changes in chromatin-interaction frequencies influence gene-regulatory mechanisms in a cell-type-specific manner. To investigate the mechanisms that govern feedback between epigenetic memory and chromatin organization,  we are looking for highly motivated students who are interested in fundamentally interdisciplinary research that spans the fields of gene regulation, developmental biology, and physics.