Principal Investigator Laurie Ann Boyer
Chromatin structure and composition play an important role in regulating gene expression and cellular identity. How active and silent chromosomal domains are assembled and propagated during development is not well understood. ES cell chromatin is generally characterized by an open, nuclease-sensitive conformation and by the dynamic association of histones and associated proteins. Chromatin reorganization and heterochromatin formation is essential for the establishment of new heritable gene expression states that accompany lineage specification. The mechanisms that control these processes, however, are poorly understood.
Heterochromatin is a major component of all metazoan genomes and regulates many processes including chromosome segregation, nuclear organization, and transcriptional gene silencing. Heterochromatin comprises large “constitutive” domains, such as pericentric regions, that are thought to be critical for chromosome segregation and genome integrity. Heterochromatin can also be assembled as more discrete domains in the promoter regions of autosomal genes during gene silencing or can encompass an entire chromosome as in the process of X-inactivation (facultative heterochromatin). Heterochromatin has been particularly refractory to study in mammalian systems because of the complexity and intricate regulation of this structure. It is our goal to functionally characterize the factors involved in regulating heterochromatin formation during development and differentiation and to understand how this structure influences genomic integrity, gene regulation, and ultimately cell fate.