Untangling the intrinsic properties of the heterochromatin spreading reaction

10 June 2016

Bassem Al-Sady
Department of Microbiology and Immunology
UC San Francisco School of Medicine


All multicellular eukaryotes achieve diverse cellular identities with the same genetic material by partitioning their genomes, such that programs irrelevant to a particular cell type are heritably repressed. The engine driving partitioning is an ultrastructure called heterochromatin, which nucleates at constitutive sites and then invades and represses chromosome domains by a polymer-type reaction called "spreading". Over many decades, powerful molecular genetics tools have uncovered and dissected the parts necessary to enact gene-repression and epigenetic propagation of heterochromatin. However, the intrinsic properties and cellular regulation of the spreading ultrastructure, central to the genome partitioning activity of heterochromatin, have received less attention. This ultrastructure differs from other cellular polymers such as the cytoskeleton in that its growth is template guided, occurring on long stretches of chromatin. The chromatin template itself constrains the system with its own structural dynamics. The central areas of interest in my lab are the mechanisms driving growth of this ultrastructure and the cellular regulatory architecture tuning its intrinsic properties to achieve stable epigenetic behavior. I will discuss approaches we are taking to generate data on the behavior of spreading both in vitro and in single cells, and the types of hypotheses we might be able to address concretely for the first time.

current theory lunch schedule