Nanopores suggest a negligible influence of CpG methylation on nucleosome packaging and stability

Martin Langecker, Andrey Ivankin, Spencer Carson, Shannon R.M. Kinney, Friedrich C. Simmel, Meni Wanunu

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

34 Zitate (Scopus)

Abstract

Nucleosomes are the fundamental repeating units of chromatin, and dynamic regulation of their positioning along DNA governs gene accessibility in eukaryotes. Although epigenetic factors have been shown to influence nucleosome structure and dynamics, the impact of DNA methylation on nucleosome packaging remains controversial. Further, all measurements to date have been carried out under zero-force conditions. In this paper, we present the first automated force measurements that probe the impact of CpG DNA methylation on nucleosome stability. In solid-state nanopore force spectroscopy, a nucleosomal DNA tail is captured into a pore and pulled on with a time-varying electrophoretic force until unraveling is detected. This is automatically repeated for hundreds of nucleosomes, yielding statistics of nucleosome lifetime vs electrophoretic force. The force geometry, which is similar to displacement forces exerted by DNA polymerases and helicases, reveals that nucleosome stability is sensitive to DNA sequence yet insensitive to CpG methylation. Our label-free method provides high-throughput data that favorably compares with other force spectroscopy experiments and is suitable for studying a variety of DNA-protein complexes.

OriginalspracheEnglisch
Seiten (von - bis)783-790
Seitenumfang8
FachzeitschriftNano Letters
Jahrgang15
Ausgabenummer1
DOIs
PublikationsstatusVeröffentlicht - 14 Jan. 2015

Fingerprint

Untersuchen Sie die Forschungsthemen von „Nanopores suggest a negligible influence of CpG methylation on nucleosome packaging and stability“. Zusammen bilden sie einen einzigartigen Fingerprint.

Dieses zitieren