Statistical and Biological Physics

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Toward a unified physical model of nucleosome patterns flanking transcription start sites

Wolfram Möbius, Brendan Osberg, Alexander M. Tsankov, Oliver J. Rando, Ulrich Gerland

The genomes of all eukaryotic organisms are highly packaged into a dynamic structure termed chromatin. On the lowest level of packaging, the structure consists of a "beads-on-a-string" arrangement, where nucleosome "particles" are connected by free DNA "linkers". A large body of recent experimental and theoretical work suggests that this structure can be appropriately described, on a coarse-grained physical level, within the theory of 1D interacting gas systems. In this work, we study which properties are required of such an interacting gas model to yield a "unified" description of nucleosome patterns in different species.

We find that the species-to-species variation of the patterns cannot be naturally explained within the simplest 1D interacting gas model of impenetrable finite-size particles (often referred to as the 'Tonks gas' in statistical physics). However, including the previously characterized biophysical property of "nucleosome breathing" – transient unwrapping of DNA segments from the histone core driven by thermal fluctuations – leads to a simple physical interpretation of the observed patterns as an interacting gas of compressible particles. Furthermore, a minimal model extension by one remodeler enzyme mechanism yields an “active nucleosome gas” which can rationalize experimental observations at reduced histone-DNA-ratio and remodeler knockouts. Taken together, our results establish a basis for a physical description of nucleosome patterns, which can serve as a null model for sequence-specific effects at individual genes and models of transcription regulation.

Picture credit: Christoph Hohmann, Media Designer for the Nanosystems Initiative Munich Excellence Cluster