Project Information
Title:
A bifunctional role for the UHRF1 UBL domain for controlling hemi-methylated DNA-dependent histone ubiquitylation
Abstract:
DNA methylation patterns, which regulate gene expression programs, are maintained
through a highly coordinated process orchestrated by the RING E3 ubiquitin ligase UHRF1.
UHRF1 controls DNA methylation inheritance by reading epigenetic modifications to histones
and DNA that activate histone H3 ubiquitylation. Here, we find that all five domains of UHRF1,
including the previously uncharacterized ubiquitin-like domain (UBL), cooperate for hemi-
methylated DNA-dependent H3 ubiquitin ligation. Our structural and biochemical studies,
including mutations found in cancer genomes, reveal a bifunctional requirement for the UBL in
histone modification: (1) the UBL, and not the RING domain, is the primary E2-recognition
domain for UHRF1 and (2) the UBL domain coordinates with other UHRF1 domains that
recognize epigenetic marks on DNA and histone H3 to direct ubiquitin to H3. Finally, we show
UBLs from other E3s also have a conserved interaction with the E2, Ube2D, highlighting the
potential prevalence of interactions between UBLs and E2s.
Notes:
This page provides public access to data associated with DaRosa et al. (2018).
