Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Friday Speaker Abstracts

CONTRIBUTIONS OF NUCLEOSOME ARCHITECTURE TO LONG-RANGE COMMUNICATION ON CHROMATIN Wilma K. Olson 1 ; 1 Rutgers, the State University of New Jersey, Chemistry and Chemical Biology, Piscataway, New Jersey, United States Although many factors participate in transcription, understanding how DNA enhancers activate the production of RNA at distant promoter sites remains a mystery. New experimental studies of transcription on well-defined chromatin arrays by the Vasily Studitsky group in combination with base-pair level simulations of protein-decorated DNA from our laboratory are making it possible to dissect these mechanisms. The combination of computation with experiment suggests that internucleosomal interactions involving the histone tails are essential for highly efficient enhancer-promoter communication and that transient internucleosomal interactions mediate distant associations between enhancers and promoters on chromatin. Ensembles of modeled structures consistent with the observed transcript levels exhibit very different three-dimensional features upon repositioning or modification of the nucleosomes placed between the sites of regulatory protein binding. The positions/spacing of the nucleosomes, the mode of DNA entry/exit, the torsional stress imposed on DNA, and the selective removal of histone tails have critical effects on the spatial properties of the simulated oligonucleosome constructs. The ‘local’ structures and deformabilities of the nucleosomes in these model systems, in turn, influence the folding and interactions of longer stretches of chromatin. Reliable treatment of long-range interactions on long stretches of chromatin, however, requires knowledge of the configurational properties of numerous oligonucleosome arrays as well as improved understanding of the proteins that mediate these looped structures.

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