Probing the Effect of Ubiquitinated Histone on Mononucleosomes by Translocation Dynamics Study through Solid-State Nanopores

Autor: Rui Hu, Cuifang Liu, Wenlong Lu, Guanghao Wei, Dapeng Yu, Wei Li, Ping Chen, Guohong Li, Qing Zhao
Rok vydání: 2022
Předmět:
Zdroj: Nano letters. 22(3)
ISSN: 1530-6992
Popis: Post-translational modifications (PTMs), such as ubiquitination, are critically important in regulating genetic expressions by adjusting the nucleosome stability. A fast and label-free technology inspecting dynamic nucleosome structures can facilitate the interrogation of PTMs effects. Here we leverage the advantages of mechanically stable solid-state nanopores and detect the effect of a ubiquitinated histone on mononucleosomes at the single-molecule level. By comparing the translocation dynamics of natural and cross-linked mononucleosomes, we verified that the nucleosomal DNA unravelled from histones in natural mononucleosomes. Furthermore, we found that a turning point of voltage corresponds to the onset of nucleosome rupture. More importantly, we reveal that ubH2A stabilizes the nucleosome by shifting the turning point to a larger value and investigated the effect of ubiquitination on different histones (ubH2A and ubH2B). These findings open promising possibilities for developing a miniaturized and portable device for the fast screening of PTMs on nucleosomes.
Databáze: OpenAIRE