Special Biological Chemistry Seminar, Yael David, Princeton University

Dec 4, 2015 at - | Carolyn Hoff Lynch Room

Inquires please contact Camille Pride at campride@sas.upenn.edu


Title:    Chemistry on Chromatin: Modifying Histones In Vivo Using Protein Trans-Splicing



Eukaryotic DNA is packaged by basic histone proteins into a higher order complex known as chromatin. Covalent chemical modifications to both DNA and histones allow chromatin to act as a dynamic signaling platform that regulates access to genomic information and ultimately establishes and maintains cellular transcriptional output. Consequently, aberrant chromatin signaling is associated with many diseases, especially cancer. A full understanding of each signaling event in isolation, and their interconnectivity, is a prerequisite to the design of next-generation therapeutic agents that act to ameliorate conditions with underlying epigenetic misregulation. However, given the complex nature of the nuclear milieu, it is extremely difficult to deconvolute specific epigenetic functions. In my talk I will describe a novel approach to this challenge, which utilizes protein chemistry to generate modified semi-synthetic histones in live cells. Applying the precision and flexibility of chemistry to native cellular chromatin allows for a new level of understanding of the local and global roles different histone post-translational modifications play in vivo.