biostudies-literatureUnknownFunabiki HNIGMS NIH HHS5-Methylcytosine (5mC) and DNA methyltransferases (DNMTs) are broadly conserved in eukaryotes but are also frequently lost during evolution. The mammalian SNF2 family ATPase HELLS and its plant ortholog DDM1 are critical for maintaining 5mC. Mutations in HELLS, its activator CDCA7, and the <i>de novo</i> DNA methyltransferase DNMT3B, cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a genetic disorder associated with the loss of DNA methylation. We here examine the coevolution of CDCA7, HELLS and DNMTs. While DNMT3, the maintenance DNA methyltransferase DNMT1, HELLS, and CDCA7 are all highly conserved in vertebrates and green plants, they are frequently co-lost in other evolutionary clades. The presence-absence patterns of these genes are not random; almost albioRxiv : the preprint server for biology2023.01.30.526367https://www.ebi.ac.uk/biostudies/studies/S-EPMC9915587biostudies-literatureCoevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases.PMC9915587R35 GM132111Jia QLuo JDFunabiki HWassing IECarroll TfalseCoevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases.5-Methylcytosine (5mC) and DNA methyltransferases (DNMTs) are broadly conserved in eukaryotes but are also frequently lost during evolution. The mammalian SNF2 family ATPase HELLS and its plant ortholog DDM1 are critical for maintaining 5mC. Mutations in HELLS, its activator CDCA7, and the <i>de novo</i> DNA methyltransferase DNMT3B, cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a genetic disorder associated with the loss of DNA methylation. We here examine the coevolution of CDCA7, HELLS and DNMTs. While DNMT3, the maintenance DNA methyltransferase DNMT1, HELLS, and CDCA7 are all highly conserved in vertebrates and green plants, they are frequently co-lost in other evolutionary clades. The presence-absence patterns of these genes are not random; almost al2023-01-01T00:00:00Z2023 Aug2026-06-27T03:20:16.726Z2025-02-19T02:23:50.071ZS-EPMC99155873677848210.1101/2023.01.30.526367