Structural basis for E3 ubiquitin ligase UHRF1 binding to nucleosome core particle and histone H3 ubiquitination.

ABSTRACT: 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 pa

SUBMITTER: Shikimachi R 

PROVIDER: S-EPMC12704277 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature