Model of Extended Chromatin
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Model of Extended Chromatin

July 3, 2012
A model of extended chromatin in which nucleosomes (red beads) are widely spaced on a segment of DNA (tubes). Loose packing yields much more irregular structure than observed in the model of condensed chromatin. In either structure, nucleosomes that are particularly stable (that is, have a strong preference for a particular sequence location) can alter the overall placement of nucleosomes and the structure of chromatin. [See related image Here.] More About This Image Five tandem repeats of the mouse mammary tumor virus promoter sequence are used to illustrate how DNA sequence affects the structure of chromatin. In each image the tube-like model represents 7444 base pairs of DNA and the large spheres represent histone octamers. Each octamer wraps about 146 base pairs of DNA into ~1.7 left-handed superhelical turns. The individual histone DNA complexes are termed nucleosomes. Nucleosome formation is the primary molecular mechanism for compacting DNA in eukaryotic organisms. These images represent two extremes of chromatin structure. At one extreme (blue histones), the sequence has no effect on the location of the individual nucleosomes. The nucleosomes assume a more or less regular spacing along the DNA. This allows for tight packing and optimal nucleosome-nucleosome interaction. In this state it is the sequence-specific properties of the linker DNA between nucleosomes that governs the gross structure of chromatin. For this particular sequence the linker DNA affects an overall bend of the chromatin fiber. At the other extreme (red histones), the DNA sequence dictates nucleosome positioning. In this case the individual histone-DNA free energies are optimized at the expense of nucleosome-nucleosome interactions. The length of linker DNA between nucleosome varies considerably. The structure shown corresponds to 70 percent occupancy by nucleosomes. At this level of occupancy the structure is extended, and allows access to other DNA-binding proteins. Long lengths of linker DNA between nucleosomes are sufficiently flexible to avoid steric overlap between nucleosomes. (Minimization not implemented so as to highlight difficulty with positioning based only on sequence.) A graduate student working on this project and the molecular modeling workflows were funded in part by a grant from the National Science Foundation (EPS 07-01491, "Louisiana's Research Infrastructure Improvement Strategy"). Additional funding was provided by the National Institutes of Health (grant 5R01GM076356) and computer resources through TeraGrid Allocation TG-MCB100111, both awarded to Thomas Bishop of the Center for Computational Science, Tulane University. Simulations done at the National Center for Supercomputing Applications. Credit: Thomas C. Bishop, Depts. Chemistry and& Physics, Louisiana Tech University

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