Section on Chromatin and Gene Expression

Head: David J. Clark

Gene activation involves the regulated recruitment of factors to a promoter in response to appropriate signals, ultimately resulting in the formation of an initiation complex by RNA polymerase II as well as in transcription. These events must occur in the presence of nucleosomes, which are compact structures capable of blocking transcription at every step. To circumvent the chromatin block, eukaryotic cells possess chromatin-remodeling and nucleosome-modifying complexes. The former (e.g., the SWI/SNF complex) use ATP to drive conformational changes in nucleosomes and to slide nucleosomes along DNA. The latter contain enzymatic activities (e.g., histone acetylases) that modify the histones post-translationally to mark them for recognition by other complexes. Geneticists have described many interesting connections between chromatin components and transcription, but a model system in which to investigate these phenomena has been lacking. We have developed such a model system, involving native plasmid chromatin purified from the yeast Saccharomyces cerevisiae, to perform high-resolution studies of the chromatin structures of active and inactive genes. Remarkably, the studies reveal that activation correlates with large-scale movements of nucleosomes and conformational changes within nucleosomes over entire genes. Our current work focuses on the roles of chromatin remodeling and histone acetylation in gene regulation.

Resources

• Employee Listing
• E-Mail the Lab: djclark@helix.nih.gov
• UCGE Home Page