Authors: Nicolas Clauvelin1, Wilma K. Olson1, Vasily Studitsky2,3.
1Rutgers University, Piscataway, NJ, USA,
2UMDNJ, Piscataway, NJ, USA
3Robert Wood Jonhson Medical School, Piscatway, NJ, USA.
Communication between sequentially distant sites along DNA is important in gene regulation and expression. These long-range interactions require deformations of the DNA, such as its tight wrapping around nucleosomes in chromatin. Indeed, the observed communication between transcription factors bound to widely spaced sites along nucleosome-decorated DNA is markedly greater than that along free DNA. In order to gain insight into how histone proteins and the constituent DNA contribute to these effects, we have developed a simple, structurally based model of chromatin and performed Monte Carlo simulations of nucleosome-decorated DNA chains. Our coarse-grained representation takes account of the local structure and deformability of histone-bound and free (linker) DNA at the base-pair level and the electrostatic interactions of representative DNA and amino acid atoms. We can then extract from our simulations the variation in global chromatin properties, such as the end-to-end distance and fiber radius, for DNA linker lengths at single base-pair resolution. Our model also makes it possible to simulate chromatin with or without nucleosome histone tails and hence to study their effects on the chromatin local structure and global properties. The simulated probabilities of long-range contacts mirror the enhancement of gene expression induced by the histone tails observed in recent experiments performed on model biochemical systems. Our structure-based model makes it possible to relate specific changes in the chromatin local structure to global properties of the fluctuating fibers. For example, we have found that long-distance communication depends not only on the flexibility of the fiber but also on the local arrangement of the nucleosomes. We also perform a detailed analysis of the inter-nucleosome interactions in order to unravel the details of distant communication on DNA as well as to develop a simpler coarse-grained model of chromatin applicable to the study of longer, biologically relevant fragments.
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