Functional Chromosomal Interactions

Recent advances have led to complete genome sequences for an increasing number of organisms. In contrast, for any single organism we understand significantly less about how these sequences and the chromosomes they compose are arranged within the nucleus.  We also do not understand how the positions of individual genetic loci respond to or establish changes in gene expression. 

It is increasingly clear that nuclear location does, indeed, matter (Cell 132:929). However, studying single loci in isolation is not sufficient to gain a complete understanding of the contribution of nuclear organization to gene expression.  Therefore it is necessary to determine spatial relationships between genetic elements as they occur in vivo.  Spatial relationships between genetic elements are most commonly determined using a technique called chromosome conformation capture (3C) (Science 295:1306).

The compact and well-annotated genome of the unicellular model eukaryote Saccharomyces cerevisiae makes it well suited for 3C analysis.  Additionally, years of careful study have precisely measured changes in transcriptional output due to treatment of S. cerevisiae with exogenous factors.  We hope to couple 3C and high throughput DNA sequencing technologies to determine how the relative positions of a subset of loci change in response to transcriptional activation.

•Kevin Schultz