Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Statistical mechanics of nucleosome crowding in yeast
Alexandre Morozov

Last modified: 2014-06-09


Eukaryotic genomes are organized into arrays of nucleosomes. Each nucleosome consists of up to 147 base pairs (bp) of genomic DNA wrapped around
a histone octamer core. The resulting complex of DNA with histones and other regulatory and structural proteins forms a multi-scale structure
called chromatin. Nucleosomal DNA may transiently peel off the histone octamer surface due to thermal fluctuations or interactions with chromatin
remodelers. Thus neighboring nucleosomes may invade each other's territories through DNA unwrapping and translocation, or through initial assembly
in partially wrapped states. Indeed, a recent high-resolution map of inter-nucleosome distances in baker's yeast (S. cerevisiae) has revealed
that at least 25% of all nucleosomes overlap DNA territories of their neighbors.
The average length of wrapped DNA follows a stereotypical pattern: nucleosomes tend to be more unwrapped in promoters and less unwrapped
in coding regions. To explain these observations, we have developed a statistical mechanics model of nucleosome unwrapping which employs
a 10-11 bp periodic histone-DNA binding energy profile. Our model is in agreement with the observed genome-wide distributions of inter-dyad distances,
wrapped DNA lengths, and nucleosome occupancies. Furthermore, our approach explains earlier in vitro measurements of accessibility
of nucleosome-covered target sites and nucleosome-induced cooperativity between DNA-binding factors. We rule out several previously
proposed scenarios of histone-DNA interactions as inconsistent with the genomic data. The surprising extent of nucleosome crowding
in yeast suggests that its treatment should be included in all future models of nucleosome positioning and energetics.