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 compl..., , , **Data from: CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes**

[https://doi.org/10.5061/dryad.s4mw6m9fc](https://doi.org/10.5061/dryad.s4mw6m9fc)

This submission contains the raw image data files supporting the manuscript accepted for publication in Science Advances (Wassing et al). The data include image data of SDS-PAGE and  native PAGE analyses (Coomassie Staining, Western blotting, and DNA staining). It also contains data spreadsheets (.xlsx files) for quantitation analysis. For detailed experimental procedures, materials, and the context, please read Wassing et al (2024) Science Advances (doi; 10.1126/sciadv.adp5753).

**Description of the data and file structure**

**Supporting files for Fig. 1A**

Fig_1A.zip includes the raw tif files of all three replicates of the DNA bead pull-down experiment shown in Fig 1A-C. Magnetic beads coupled with double-stranded 54 bp DNA oligos containing unmethylated CpGs (un-Me), fully methylated CpGs (full-Me), or hem...