Genome-wide localization of a chromatin-remodeling factor demonstrates its role in orchestrating the transcriptional program of the TOR signaling pathway

Marc Damelin
Dana-Farber Cancer Institute
Smith Building 922
44 Binney Street
Boston, MA 02115
telephone: (617) 632-5104
fax: (617) 632-5103
email: damelin@fas.harvard.edu
prestype: Platform
presenter: Marc Damelin

Marc Damelin (1,2), Itamar Simon (3), Frederick P. Roth (1), Richard A. Young (3), Bradley R. Cairns (4), and Pamela A. Silver (1,2)

(1) Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
(2) The Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.
(3) Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142.
(4) Howard Hughes Medical Institute and Department of Oncological Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112.

We have found that the RSC chromatin-remodeling complex in Saccharomyces cerevisiae coordinates programs of gene expression regulated by the TOR pathway, which regulates cell growth in response to nutrient availability and stress. The connection became evident from the genome-wide localization of Rsc9, a novel RSC component. The experiment explores protein-DNA interactions at the genomic level by combining chromatin immunoprecipitation and microarray analysis (Ren et al., 2000), and has enabled us to identify the sites of RSC occupancy throughout the genome.

Our analysis of Rsc9-occupied sites focused on detecting over-representations of genes in categories defined by a given attribute, such as a biochemical function or subcellular localization. We noticed that several categories that are significantly enriched among Rsc9-occupied sites are comprised of genes transcriptionally regulated by TOR signaling. Indeed, treatment of cells with rapamycin, which specifically affects the TOR pathway, resulted in dramatic genome-wide changes in Rsc9 localization. Northern analysis demonstrated that Rsc9 both represses and activates transcription regulated by TOR, consistent with its rapamycin-induced redistribution. We conclude that RSC is directly involved in the transcriptional program directed by the TOR pathway. Our results illustrate the strength of functional genomics in revealing relationships between distinct cellular processes.