280350 Recovery of Chromosome Structural Ensembles From Contact Probabilities

Tuesday, October 30, 2012: 1:42 PM
Westmoreland East (Westin )
Dario Meluzzi, Department of NanoEngineering, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA and Gaurav Arya, Department of Nanoengineering, University of California, San Diego, La Jolla, CA

Chromatin is a complex filamentous assembly of DNA and histone proteins that fills the nucleus of eukaryotic cells. The higher-order folding of chromatin into chromosomes is thought to play important roles in regulating vital genomic processes, such as transcription, replication, recombination, and DNA repair. However, the specific spatial organization of chromatin within the nucleus and the effects of this organization on the above processes are not well understood. Recently, an elaborate set of experimental techniques known as Chromosome Conformation Capture (3C) have allowed researchers to measure the frequency of interactions between different fragments of the chromatin fiber in vivo, providing the first glimpse into the complex looping interactions present inside chromosomes. Here we present a computational approach for inferring an ensemble of chromatin configurations from such interaction frequencies. In particular, we perform simulations of the chromatin fiber to measure probabilities of contact between different parts of the fiber and we restrain the fiber to match a given set of known contact probabilities. Using this approach we are able to recover known spatial measures for a number of artificial systems of increasing complexity. We are next applying this method to deduce ensembles of chromatin structure consistent with 3C experimental data.

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