Nucleosomes regulate base-specific mutations in eukaryotes

How spontaneous mutations are regulated is an important but poorly understood question. Theoretical examinations motivate us to hypothesize that in eukaryotic genomes nucleosomal DNA undergoes fewer C->T mutations because of suppressed cytosine hydrolytic deamination than nucleosome-depleted DNA. Using comparative genomic analyses and an in vitro evolution experiment, we validate this hypothesis and show that nucleosome occupancy can nearly completely eliminate cytosine deamination, resulting in ~50% decrease of the C->T mutation rate in nucleosomal DNA.