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Cited by 19Genomics and Chromatin DynamicsUbiquitin and proteasome pathwaysChromatin Remodeling and Cancer

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Structure of the human Bre1 complex bound to the nucleosome

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Onishi, Shuhei, Uchiyama, Kotone, Sato, Ko, Okada, Chikako, Kobayashi, Shunsuke, Hamada, Keisuke, Nishizawa, Tomohiro, Nureki, Osamu, Ogata, Kazuhiro, Sengoku, Toru·2024·Nature Communications
DOI 10.1038/s41467-024-46910-8PMC PMC10959955

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Abstract

Histone H2B monoubiquitination (at Lys120 in humans) regulates transcription elongation and DNA repair. In humans, H2B monoubiquitination is catalyzed by the heterodimeric Bre1 complex composed of Bre1A/RNF20 and Bre1B/RNF40. The Bre1 proteins generally function as tumor suppressors, while in certain cancers, they facilitate cancer cell proliferation. To obtain structural insights of H2BK120 ubiquitination and its regulation, we report the cryo-electron microscopy structure of the human Bre1 complex bound to the nucleosome. The two RING domains of Bre1A and Bre1B recognize the acidic patch and the nucleosomal DNA phosphates around SHL 6.0–6.5, which are ideally located to recruit the E2 enzyme and ubiquitin for H2BK120-specific ubiquitination. Mutational experiments suggest that the two RING domains bind in two orientations and that ubiquitination occurs when Bre1A binds to the acidic patch. Our results provide insights into the H2BK120-specific ubiquitination by the Bre1 proteins and suggest that H2B monoubiquitination can be regulated by nuclesomal DNA flexibility.

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Metadata

Authors
Onishi, S., Uchiyama, K., Sato, K., Okada, C., Kobayashi, S., Hamada, K., Nishizawa, T., Nureki, O., Ogata, K., & Sengoku, T.
Affiliations
  • Yokohama City University (JP)
  • The University of Tokyo (JP)
Corresponding author
  • Ogata, Kazuhiro
  • Sengoku, Toru
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-03-22
Volume
15
Issue
1
Pages
2580-2580
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-024-46910-8
PMC
PMC10959955
OpenAlex
W4393082244
Cited by
19
References
5
Citations by year
2026: 7 · 2025: 8 · 2024: 4
FWCI
2.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
MEXT | Japan Society for the Promotion of Science (21H05161)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
RNF20, RNF40, histone H2B monoubiquitination, nucleosome, RING domain, acidic patch, transcription elongation, DNA repair, tumor suppressor, cryo-EM structure
MeSH terms
DNA, Histones, Humans, Neoplasms, Nucleosomes, Cryoelectron Microscopy, Ubiquitin-Protein Ligases, Ubiquitination

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