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TitleStructural basis for E3 ubiquitin ligase UHRF1 binding to nucleosome core particle and histone H3 ubiquitination.
Journal, issue, pagesJ Biol Chem, Vol. 301, Issue 12, Page 110894, Year 2025
Publish dateNov 4, 2025
AuthorsReia Shikimachi / Shun Matsuzawa / Hiroki Onoda / Tsuyoshi Konuma / Atsushi Yamagata / Mikako Shirouzu / Kosuke Yamaguchi / Kyohei Arita /
PubMed AbstractThe maintenance of DNA methylation in differentiated cells is regulated by a ubiquitin signal generated by UHRF1 (ubiquitin-like with plant homeodomain and RING finger domain 1), which plays a ...The maintenance of DNA methylation in differentiated cells is regulated by a ubiquitin signal generated by UHRF1 (ubiquitin-like with plant homeodomain and RING finger domain 1), which plays a pivotal role in recruitment of DNA methyltransferase DNMT1 to hemimethylated CpG sites. UHRF1 catalyzes multiple monoubiquitinations on histone H3 within nucleosomes. However, the structural mechanisms underlying the binding of UHRF1 to nucleosomes and the subsequent formation of the ubiquitin signal remain incompletely understood. Here, we report cryo-EM structures of UHRF1 bound to nucleosome core particle (NCP) harboring H3K9me3 and a single hemimethylated CpG site. The structures of the UHRF1-NCP complexes reveal an unanticipated interaction between the UHRF1 tandem Tudor domain and the acidic patch of the NCP. This interaction enhances histone H3 ubiquitination and stabilizes UHRF1 binding to the NCP in a manner that is dependent on the position of the hemimethylated CpG site. These findings provide mechanistic insights into the binding of UHRF1 to the NCP and the multiple monoubiquitination of histone H3 within the NCP.
External linksJ Biol Chem / PubMed:41197730 / PubMed Central
MethodsEM (single particle)
Resolution2.65 - 2.88 Å
Structure data

EMDB-39541: Cryo-EM map of UHRF1 in complex with nucleosome containing hemimethylated CpG site at 5'linker DNA
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-39548: Cryo-EM map of UHRF1 in complex with nucleosome containing hemimethylated CpG site at 3'linker DNA
Method: EM (single particle) / Resolution: 2.88 Å

EMDB-39550: Cryo-EM map of UHRF1 in complex with nucleosome containing hemimethylated CpG site at widom601 sequence
Method: EM (single particle) / Resolution: 2.85 Å

Source
  • Homo sapiens (human)

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