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Nucleosomal DNA unwinding pathway through canonical and non-canonical histone disassembly.
Nozawa, Hikaru; Nagae, Fritz; Ogihara, Satoshi; Hirano, Rina; Yamazaki, Hirohito; Iizuka, Ryo; Akatsu, Munetaka; Kujirai, Tomoya; Takada, Shoji; Kurumizaka, Hitoshi; Uemura, Sotaro.
Afiliación
  • Nozawa H; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Nagae F; Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan.
  • Ogihara S; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Hirano R; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Yamazaki H; Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
  • Iizuka R; Top Runner Incubation Center for Academia-Industry Fusion, Nagaoka University of Technology, Nagaoka, Niigata, Japan.
  • Akatsu M; Department of Mechanical Engineering, Nagaoka University of Technology, Nagaoka, Niigata, Japan.
  • Kujirai T; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Takada S; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Kurumizaka H; Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
  • Uemura S; Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.
Commun Biol ; 7(1): 1144, 2024 Sep 14.
Article en En | MEDLINE | ID: mdl-39277674
ABSTRACT
The nucleosome including H2A.B, a mammalian-specific H2A variant, plays pivotal roles in spermatogenesis, embryogenesis, and oncogenesis, indicating unique involvement in transcriptional regulation distinct from canonical H2A nucleosomes. Despite its significance, the exact regulatory mechanism remains elusive. This study utilized solid-state nanopores to investigate DNA unwinding dynamics, applying local force between DNA and histones. Comparative analysis of canonical H2A and H2A.B nucleosomes demonstrated that the H2A.B variant required a lower voltage for complete DNA unwinding. Furthermore, synchronization analysis and molecular dynamics simulations indicate that the H2A.B variant rapidly unwinds DNA, causing the H2A-H2B dimer to dissociate from DNA immediately upon disassembly of the histone octamer. In contrast, canonical H2A nucleosomes unwind DNA at a slower rate, suggesting that the H2A-H2B dimer undergoes a state of stacking at the pore. These findings suggest that nucleosomal DNA in the H2A.B nucleosomes undergoes a DNA unwinding process involving histone octamer disassembly distinct from that of canonical H2A nucleosomes, enabling smoother unwinding. The integrated approach of MD simulations and nanopore measurements is expected to evolve into a versatile tool for studying molecular interactions, not only within nucleosomes but also through the forced dissociation of DNA-protein complexes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Histonas / Nucleosomas / Simulación de Dinámica Molecular Límite: Animals Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Histonas / Nucleosomas / Simulación de Dinámica Molecular Límite: Animals Idioma: En Revista: Commun Biol Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido