The packaging of DNA in chromatin greatly influences gene expression. Recent findings indicate that chromatin positioning within the nucleus influences gene activity. In particular, the nuclear periphery appears to comprise a domain critical for transcriptional control. Many highly expressed genes localize to nuclear pores. Silenced chromatin also occupies a specific nuclear address. In yeast and in higher eukaryotes, silenced chromatin resides in sub-compartments at the nuclear periphery. In humans, some mutation of lamins, genes that contribute to the nuclear compartmentalization of chromatin, lead to laminopathies, including muscular dystrophy and Hutchinson-Gilford Progeria Syndrome. The goal of this proposal is to understand how chromatin organization is determined using yeast Saccharomyces as a model system. The Gartenberg lab recently showed that yeast heterochromatin is bound to the nuclear periphery by a nuclear membrane-associated protein Esc1.
I aim to identify Esc1 interacting partners by adapting the split ubiquitin yeast two hybrid screen and by using and a whole genome cytological screen. I will then use silencing and DNA localization assays to learn how Esc1 contributes to the nuclear position and regulation of genes.
|Park, Sookhee; Patterson, Erin E; Cobb, Jenel et al. (2011) Palmitoylation controls the dynamics of budding-yeast heterochromatin via the telomere-binding protein Rif1. Proc Natl Acad Sci U S A 108:14572-7|