Data from: CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes

Mutations of the SNF2 family ATPase HELLS and its activator CDCA7 cause
immunodeficiency, centromeric instability, facial anomalies (ICF)
syndrome, characterized by DNA hypomethylation at heterochromatin. It
remains unclear why CDCA7-HELLS is the sole nucleosome remodeling complex
whose deficiency abrogates the maintenance of DNA methylation. We here
identify the unique zinc-finger domain of CDCA7 as an evolutionarily
conserved hemimethylation-sensing zinc finger (HMZF) domain. Cryo-EM
structural analysis of the CDCA7-nucleosome complex reveals that the HMZF
domain can recognize hemimethylated CpG in the outward-facing DNA major
groove within the nucleosome core particle (NCP), whereas UHRF1, the
critical activator of the maintenance methyltransferase DNMT1, cannot.
CDCA7 recruits HELLS to hemimethylated chromatin and facilitates
UHRF1-mediated H3 ubiquitylation associated with replication-uncoupled
maintenance DNA methylation. We propose that the CDCA7-HELLS nucleosome
remodeling complex assists the maintenance of DNA methylation on chromatin
by sensing hemimethylated CpG that is otherwise inaccessible to UHRF1 and
DNMT1.