Interactive Chromatin Modeling with Genome Browser

Abstract

Nucleosomes are the fundamental structural unit of chromatin, therefore all genomic functions are influenced by nucleosome structure and dynamics. The standard nucleosome is an octasome and consists of 147 base pairs of double stranded DNA wrapped 1.7 times around eight histones. Sub-octasome (tetrasome, hexasome, hemisome) and super-octasome (chromatosome) states also exist. We have integrated our Interactive Chromatin Modeling(ICM) tools with the Dalliance genome browser (DGB) as a means of integrating physical modeling with bioinformatics. ICM is an interactive web based tool that allows users to rapidly fold any sequence of DNA into atomic or coarse grained models of chromatin. ICM-DGB is designed to unite ICM's physical modeling with informatics data obtained from public databases, e.g. experimentally or theoretically determined nucleosome positions. ICM-DGB currently allows users to manipulate nucleosome positions (add, delete and move), assign different conformational states to each nucleosome (e.g. tetrasome, octasome, chromatosome), display structural data from a model as track data in DGB (e.g. Roll, Slide or Twist) and map informatics data onto a molecular structure (e.g. nucleosome positions, DNA damage sites). Our web based implementation of ICM-DGB utilizes a coarse grained model of chromatin implemented in LAMMPS for structure relaxation and displays the model with JMol. Here we utilize experimentally determined reference maps of nucleosome positions for the Saccharomyces cerevisiae genome to assess chromatin folding for the CHA1, HIS3 and PHO5 promoters. The models demonstrate that experimentally determined nucleosome positions are insufficient to achieve tight packing of chromatin. As a tool, ICM-DGB supports cross-validation of physical modeling and informatics approaches and the ability to investigate structure-function relationships for regions of the genome ranging from kilobases to megabases.