Nucleosome Organization is Quantitatively Described by Statistical Positioning Up- and Downstream of Transcription Start Sites

Abstract

The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which parts are not. A salient feature in recent genome-wide nucleosome maps is that nucleosomes appear well-positioned around a nucleosome free region (NFR) just upstream from the transcription start site (TSS). What determines this nucleosome organization is not known. One scenario is that the majority of nucleosome positions near the TSS are directly encoded in the DNA sequence. The alternative “statistical positioning” scenario, is that a few local barriers on the genome strongly constrain the positions of closeby nucleosomes, purely on statistical grounds. We use a physical model for the latter scenario, based on the Tonks gas of statistical physics, to quantitatively analyze recent data for yeast. We find that although the typical patterns on the two sides of the TSS are different, they are both quantitatively described by the same physical model, with the same parameters, but different boundary conditions. The inferred boundary conditions suggest that the first nucleosome downstream from the NFR is typically directly positioned while the first nucleosome upstream is statistically positioned via a nucleosome-repelling DNA region.