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