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Mutations in these genes cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, which also results in DNA hypomethylation of satellite repeat regions. We investigated the functional domains of human CDCA7 in HELLS using several mutant CDCA7 proteins. The central region is critical for binding to HELLS, activation of ATPase, and nucleosome sliding activities of HELLS-CDCA7. The N-terminal region tends to inhibit ATPase activity. The C-terminal 4CXXC-type zinc finger domain contributes to CpG and hemimethylated CpG DNA preference for DNA-dependent HELLS-CDCA7 ATPase activity. Furthermore, CDCA7 showed a binding preference to DNA containing hemimethylated CpG, and replication-dependent pericentromeric heterochromatin foci formation of CDCA7 with HELLS was observed in mouse embryonic stem cells; however, all these phenotypes were lost in the case of an ICF syndrome mutant of CDCA7 mutated in the zinc finger domain. Thus, CDCA7 most likely plays a role in the recruitment of HELLS, activates its chromatin remodeling function, and efficiently induces DNA methylation, especially at hemimethylated replication sites.<\/jats:p>","DOI":"10.1093\/nar\/gkae677","type":"journal-article","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:06:02Z","timestamp":1723680362000},"page":"10194-10219","source":"Crossref","is-referenced-by-count":24,"title":["The C-terminal 4CXXC-type zinc finger domain of CDCA7 recognizes hemimethylated DNA and modulates activities of chromatin remodeling enzyme HELLS"],"prefix":"10.1093","volume":"52","author":[{"given":"Akeo","family":"Shinkai","sequence":"first","affiliation":[{"name":"Cellular Memory Laboratory , RIKEN Cluster for Pioneering Research, Wako City , Saitama\u00a0 351-0198 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideharu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Thomas Jefferson University , Philadelphia , PA, 19107,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikako","family":"Shimura","sequence":"additional","affiliation":[{"name":"Cellular Memory Laboratory , RIKEN Cluster for Pioneering Research, Wako City , Saitama\u00a0 351-0198 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Cellular Memory Laboratory , RIKEN Cluster for Pioneering Research, Wako City , Saitama\u00a0 351-0198 , Japan"},{"name":"Division of Life Science, Graduate School of Science & Engineering, Saitama University , Shimo-Ohkubo 255, Sakura Ward, Saitama City , Saitama\u00a0 338-8570 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Faculty of Life and Environmental Sciences, University of Yamanashi , Yamanashi\u00a0 400-8510 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1842-6934","authenticated-orcid":false,"given":"Naoki","family":"Horikoshi","sequence":"additional","affiliation":[{"name":"Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo , 1-1-1 Yayoi, Bunkyo-ku, Tokyo\u00a0 113-0032 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Pluripotent Stem Cell Biology, IMEG, Kumamoto university , Honjo 2-2-1, Chuo-ku, Kumamoto , Kumamoto\u00a0 860-0811 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Niwa","sequence":"additional","affiliation":[{"name":"Department of Pluripotent Stem Cell Biology, IMEG, Kumamoto university , Honjo 2-2-1, Chuo-ku, Kumamoto , Kumamoto\u00a0 860-0811 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2587-2150","authenticated-orcid":false,"given":"Erik\u00a0W","family":"Debler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Thomas Jefferson University , Philadelphia , PA, 19107,\u00a0 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-3722","authenticated-orcid":false,"given":"Hitoshi","family":"Kurumizaka","sequence":"additional","affiliation":[{"name":"Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo , 1-1-1 Yayoi, Bunkyo-ku, Tokyo\u00a0 113-0032 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6051-2484","authenticated-orcid":false,"given":"Yoichi","family":"Shinkai","sequence":"additional","affiliation":[{"name":"Cellular Memory Laboratory , RIKEN Cluster for Pioneering Research, Wako City , Saitama\u00a0 351-0198 , Japan"},{"name":"Division of Life Science, Graduate School of Science & Engineering, Saitama University , Shimo-Ohkubo 255, Sakura Ward, Saitama City , Saitama\u00a0 338-8570 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,15]]},"reference":[{"key":"2024092307454362300_B1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/8803","article-title":"Maintenance of genomic methylation requires a SWI2\/SNF2-like protein","volume":"22","author":"Jeddeloh","year":"1999","journal-title":"Nat. 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