Nucleosome positioning stability is a modulator of germline mutation rate variation across the human genome.

ABSTRACT: Nucleosome organization has been suggested to affect local mutation rates in the genome. However, the lack of de novo mutation and high-resolution nucleosome data has limited the investigation of this hypothesis. Additionally, analyses using indirect mutation rate measurements have yielded contradictory and potentially confounding results. Here, we combine data on >300,000 human de novo mutations with high-resolution nucleosome maps and find substantially elevated mutation rates around translationally stable ('strong') nucleosomes. We show that the mutational mechanisms affected by strong nucleosomes are low-fidelity replication, insufficient mismatch repair and increased double-strand breaks. Strong nucleosomes preferentially locate within young SINE/LINE transposons, suggesting that when

SUBMITTER: Li C 

PROVIDER: S-EPMC7070026 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature