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(09-0423) Prof. Jon Widom, Cherry Emerson Lecture Series

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Prof. Jon Widom, Northwestern University

The Genomic Code for Nucleosome Positioning

Cherry Emerson Lecture Series

Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. We have 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. The physical basis of the nucleosome DNA sequences preferences lies in the sequence-dependent mechanics of DNA itself. Most recently, we showed that the distribution of nucleosomes reconstituted on genomic DNA in a purified in vitro system closely resembles the in vivo nucleosome distributions obtained in several different growth conditions. Thus, the genome's intrinsically encoded nucleosome positioning information accounts for the overwhelming majority of nucleosome-occupied versus nucleosome-depleted regions across the entire genome; condition-specific actions of gene regulatory proteins and chromatin remodeling factors lead to specific localized changes in nucleosome occupancy and positioning, leaving much of the chromatin organization unaffected. A statistical model for nucleosome positioning trained on the yeast in vitro nucleosome map is highly predictive of in vivo nucleosome occupancy patterns in yeast, C. elegans and human. 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, to regulate the expression noise characteristics of different promoters, and the replication firing characteristics of differing origins, and to define the next higher level of chromosome structure itself.

For more information contact Dr. Carrie Shepler or Ms. Natalie John.

Status

  • Workflow Status:Published
  • Created By:Shirley Tomes
  • Created:11/23/2008
  • Modified By:Fletcher Moore
  • Modified:10/07/2016

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