Prof. Katherine Albanese, Department of Chemistry, Wake Forest University, will discuss uncovering histone epigenetic biology through de novo protein design.

The hierarchical systems of epigenetics, particularly chromatin architecture, regulate DNA-templated processes. Histone posttranslational modifications maintain cell homeostasis. The specific PTM response is governed by cooperative interactions between multiple binding partners. Linking histone PTMs to elicited biological responses is challenging. Quantitative and orthogonal experiments within the nucleosome interactome are needed to understand the chemical and biophysical basis of PTMs influencing dynamic epigenetic states. We aim to develop novel de novo proteins as orthogonal tools for in vitro and cellular mechanism probing. Our de novo scaffolds selectively bind histone PTMs and diseaseassociated mutations and harness the ability to turn off and on protein-protein interactions under exogenous control. This represents a significant advancement in deconvolving transient and cooperative interactions underpinning chromatin regulation and epigenetic states. These tools and methodologies can be applied to other research questions, providing a framework for investigating other complex biological systems. Details.