Physics Colloquium, May 22, 2007
A Genomic Code for Nucleosome Positioning Jonathan Widom

Northwestern University

Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes are remarkable from a physical perspective because in each nucleosome, one persistence length of DNA - a lengthscale of DNA inflexibility - is wrapped in nearly two complete superhelical turns around a protein core. As a consequence of this extreme DNA bending, nucleosomes have higher affinity for particular DNA sequences that are best-able to sharply bend as required by the nucleosome. We discovered that genomes care where their nucleosomes are located on average, and that genomes manifest this care by encoding an additional layer of genetic information, superimposed on top of other kinds of regulatory and coding information that were previously recognized. We have developed a partial ability to read this nucleosome positioning code and predict the in vivo locations of nucleosomes. We now have two entirely independent approaches to understanding and predicting nucleosome positioning: one is based on a statistical profile of natural nucleosome DNAs, the other, on a dinucleotide mechanics model which itself derives from X-ray crystallographic studies of non-nucleosomal protein-DNA complexes. Our results suggest that genomes utilize the nucleosome positioning code to facilitate specific chromosome functions including to delineate functional versus nonfunctional binding sites for key gene regulatory proteins, and to define the next higher level of chromosome structure itself.

Dr. Widom's Web Site

4:00 p.m., Physics Research Building (PRB), Room 1080

Reception at 3:45 p.m., Atrium, PRB