Biophysical Models of Nucleosome Positioning

Abstract

A human body contains enough DNA to circle the Earth's Equator more than 2.5 million times. The basic units of DNA packaging are called nucleosomes. Their locations along the chromosomes play an essential role in gene regulation. We study nucleosome positioning in yeast, fly and mouse, and build biophysical models in order to explain the genome-wide nucleosome organization. We show that DNA sequence is not the major cause of the regular arrays of nucleosomes observed in vivo near the transcription start sites (TSS). We construct a minimal model in which nucleosomes are positioned by potential barriers located in the gene promoters, and which accurately reproduces the genome-wide nucleosome occupancy patterns observed over the transcribed regions in living cells. Our statistical mechanics model allows us to study nucleosome phasing against potential barriers and wells [1, 2], sequence-dependent nucleosome affinity [2], nucleosome unwrapping [3], competition between different DNA-binding proteins, and accessibility of transcription factors [4, 5] to target sites which are found in nucleosomal DNA, among others. We also discuss alternative nucleosome positioning mechanisms: nucleosome anchoring [6] and active nucleosome positioning by ATP-dependent remodelers [7].[1] RV Chereji, D Tolkunov, G Locke, AV Morozov, Phys. Rev. E 83, 050903 (2011)[2] RV Chereji and AV Morozov, J. Stat. Phys. 144, 379 (2011)[3] RV Chereji and AV Morozov, Proc. Natl. Acad. Sci. U.S.A. 111, 5236 (2014)[4] N Petrenko, RV Chereji, MN McClean, AV Morozov, JR Broach Mol. Biol. Cell 24, 2045 (2013)[5] N Elfving∗, RV Chereji∗, V Bharatula, S Bjorklund, AV Morozov, JR Broach, Nucleic Acids Res. 42, 5468 (2014) (∗ contributed equally)[6] RV Chereji, AV Morozov, YM Moshkin, in preparation[7] D Ganguli∗, RV Chereji∗, J Iben, HA Cole, DJ Clark, Genome Res. (2014) (∗ contributed equally)