{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:04:49Z","timestamp":1790643889375,"version":"4.1.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"crossref","award":["JP18K0691"],"award-info":[{"award-number":["JP18K0691"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"crossref","award":["JP19H05740"],"award-info":[{"award-number":["JP19H05740"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for Promotion of Science","doi-asserted-by":"crossref","award":["JP26253020"],"award-info":[{"award-number":["JP26253020"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Yamada Science Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is in most cases caused by mutations in either DNA methyltransferase (DNMT)3B, zinc finger and BTB domain containing 24, cell division cycle associated 7 or helicase lymphoid-specific. However, the causative genes of a few ICF patients remain unknown. We, herein, identified ubiquitin-like with plant homeodomain and really interesting new gene finger domains 1 (UHRF1) as a novel causative gene of one such patient with atypical symptoms. This patient is a compound heterozygote for two previously unreported mutations in UHRF1: c.886C\u2009&amp;gt;\u2009T (p.R296W) and c.1852C\u2009&amp;gt;\u2009T (p.R618X). The R618X mutation plausibly caused nonsense-mediated decay, while the R296W mutation changed the higher order structure of UHRF1, which is indispensable for the maintenance of CG methylation along with DNMT1. Genome-wide methylation analysis revealed that the patient had a centromeric\/pericentromeric hypomethylation, which is the main ICF signature, but also had a distinctive hypomethylation pattern compared to patients with the other ICF syndrome subtypes. Structural and biochemical analyses revealed that the R296W mutation disrupted the protein conformation and strengthened the binding affinity of UHRF1 with its partner LIG1 and reduced ubiquitylation activity of UHRF1 towards its ubiquitylation substrates, histone H3 and proliferating cell nuclear antigen -associated factor 15 (PAF15). We confirmed that the R296W mutation causes hypomethylation at pericentromeric repeats by generating the HEK293 cell lines that mimic the patient\u2019s UHRF1 molecular context. Since proper interactions of the UHRF1 with LIG1, PAF15 and histone H3 are essential for the maintenance of CG methylation, the mutation could disturb the maintenance process. Evidence for the importance of the UHRF1 conformation for CG methylation in humans is, herein, provided for the first time and deepens our understanding of its role in regulation of CG methylation.<\/jats:p>","DOI":"10.1093\/hmg\/ddac291","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T13:49:53Z","timestamp":1669988993000},"page":"1439-1456","source":"Crossref","is-referenced-by-count":31,"title":["Novel compound heterozygous mutations in <i>UHRF1<\/i> are associated with atypical immunodeficiency, centromeric instability and facial anomalies syndrome with distinctive genome-wide DNA hypomethylation"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9629-3818","authenticated-orcid":false,"given":"Motoko","family":"Unoki","sequence":"first","affiliation":[{"name":"Division of Epigenomics and Development, Medical Institute of Bioregulation, University of Tokyo , Fukuoka 812-8582 , Japan"},{"name":"Department of Human Genetics, School of International Health, Graduate School of Medicine, The University of Tokyo , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Velasco","sequence":"additional","affiliation":[{"name":"Epigenetics and Cell Fate, Universit\u00e9 Paris Cit\u00e9 , CNRS, Paris 75013 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Kori","sequence":"additional","affiliation":[{"name":"Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University , Kanagawa 230-0045 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyohei","family":"Arita","sequence":"additional","affiliation":[{"name":"Structural Biology Laboratory, Graduate School of Medical Life Science, Yokohama City University , Kanagawa 230-0045 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasukazu","family":"Daigaku","sequence":"additional","affiliation":[{"name":"Cancer Genome Dynamics Project, The Cancer Institute of Japanese Foundation for Cancer Research , Tokyo 135-8550 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan Kin Au","family":"Yeung","sequence":"additional","affiliation":[{"name":"Division of Epigenomics and Development, Medical Institute of Bioregulation, University of Tokyo , Fukuoka 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, School of International Health, Graduate School of Medicine, The University of Tokyo , Tokyo 113-0033 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics , Saitama Children's Medical Center, Saitama 330-8777 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Child Studies, Faculty of Child Studies, Seitoku University , Chiba 271-8555 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunio","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Yamanashi , Yamanashi 409-3898 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Epigenomics and Development, Medical Institute of Bioregulation, University of Tokyo , Fukuoka 812-8582 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"2023042013361381700_ref1","volume-title":"Recent Insights into the Mechanisms of De Novo and Maintenance of DNA Methylation in Mammals","author":"Unoki","year":"2019"},{"key":"2023042013361381700_ref2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.2183\/pjab.98.021","article-title":"The UHRF protein family in epigenetics, development, and carcinogenesis","volume":"98","author":"Unoki","year":"2022","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"2023042013361381700_ref3","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.molcel.2017.07.012","article-title":"Methylation of DNA Ligase 1 by G9a\/GLP recruits UHRF1 to replicating DNA and regulates DNA methylation","volume":"67","author":"Ferry","year":"2017","journal-title":"Mol. Cell"},{"key":"2023042013361381700_ref4","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/s41467-020-15006-4","article-title":"Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation","volume":"11","author":"Nishiyama","year":"2020","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref5","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/s41422-020-0359-9","article-title":"Kinetics and mechanisms of mitotic inheritance of DNA methylation and their roles in aging-associated methylome deterioration","volume":"30","author":"Ming","year":"2020","journal-title":"Cell Res."},{"key":"2023042013361381700_ref6","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nature12488","article-title":"Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication","volume":"502","author":"Nishiyama","year":"2013","journal-title":"Nature"},{"key":"2023042013361381700_ref7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1750-1172-1-2","article-title":"Immunodeficiency, centromeric region instability, facial anomalies syndrome (ICF)","volume":"1","author":"Ehrlich","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"2023042013361381700_ref8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1136\/jmg.25.3.173","article-title":"Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome","volume":"25","author":"Maraschio","year":"1988","journal-title":"J. Med. Genet."},{"key":"2023042013361381700_ref9","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","article-title":"DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development","volume":"99","author":"Okano","year":"1999","journal-title":"Cell"},{"key":"2023042013361381700_ref10","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/46052","article-title":"Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene","volume":"402","author":"Xu","year":"1999","journal-title":"Nature"},{"key":"2023042013361381700_ref11","doi-asserted-by":"crossref","first-page":"14412","DOI":"10.1073\/pnas.96.25.14412","article-title":"The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome","volume":"96","author":"Hansen","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2023042013361381700_ref12","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1038\/ncomms14015","article-title":"Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids","volume":"8","author":"Sagie","year":"2017","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/humu.20113","article-title":"DNMT3B mutations and DNA methylation defect define two types of ICF syndrome","volume":"25","author":"Jiang","year":"2005","journal-title":"Hum. Mutat."},{"key":"2023042013361381700_ref14","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1093\/hmg\/ddy265","article-title":"Subtelomeric methylation distinguishes between subtypes of immunodeficiency, centromeric instability and facial anomalies syndrome","volume":"27","author":"Toubiana","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2023042013361381700_ref15","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.ajhg.2011.04.018","article-title":"Mutations in ZBTB24 are associated with immunodeficiency, centromeric instability, and facial anomalies syndrome type 2","volume":"88","author":"Greef","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"2023042013361381700_ref16","doi-asserted-by":"crossref","first-page":"7870","DOI":"10.1038\/ncomms8870","article-title":"Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome","volume":"6","author":"Thijssen","year":"2015","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref17","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1093\/hmg\/ddw243","article-title":"Converging disease genes in ICF syndrome: ZBTB24 controls expression of CDCA7 in mammals","volume":"25","author":"Wu","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"2023042013361381700_ref18","doi-asserted-by":"crossref","first-page":"E876","DOI":"10.1073\/pnas.1717509115","article-title":"HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome","volume":"115","author":"Jenness","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2023042013361381700_ref19","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1172\/JCI99751","article-title":"CDCA7 and HELLS mutations undermine nonhomologous end joining in centromeric instability syndrome","volume":"129","author":"Unoki","year":"2019","journal-title":"J. Clin. Invest."},{"key":"2023042013361381700_ref20","doi-asserted-by":"crossref","first-page":"17865","DOI":"10.1038\/s41598-020-74636-2","article-title":"CDCA7 and HELLS suppress DNA:RNA hybrid-associated DNA damage at pericentromeric repeats","volume":"10","author":"Unoki","year":"2020","journal-title":"Sci. Rep."},{"key":"2023042013361381700_ref21","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1093\/hmg\/ddy130","article-title":"Comparative methylome analysis of ICF patients identifies heterochromatin loci that require ZBTB24, CDCA7 and HELLS for their methylated state","volume":"27","author":"Velasco","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"2023042013361381700_ref22","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22073735","article-title":"Interplay between histone and DNA methylation seen through comparative methylomes in rare Mendelian disorders","volume":"22","author":"Velasco","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2023042013361381700_ref23","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/ajmg.a.30135","article-title":"ICF syndrome in a girl with DNA hypomethylation but without detectable DNMT3B mutation","volume":"129A","author":"Kubota","year":"2004","journal-title":"Am. J. Med. Genet. A."},{"key":"2023042013361381700_ref24","doi-asserted-by":"crossref","first-page":"12950","DOI":"10.1073\/pnas.1203701109","article-title":"Recognition of modification status on a histone H3 tail by linked histone reader modules of the epigenetic regulator UHRF1","volume":"109","author":"Arita","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2023042013361381700_ref25","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gks454","article-title":"Amplification-free whole-genome bisulfite sequencing by post-bisulfite adaptor tagging","volume":"40","author":"Miura","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2023042013361381700_ref26","doi-asserted-by":"crossref","first-page":"10383","DOI":"10.1038\/s41598-019-46875-5","article-title":"Systematic evaluation of library preparation methods and sequencing platforms for high-throughput whole genome bisulfite sequencing","volume":"9","author":"Zhou","year":"2019","journal-title":"Sci. Rep."},{"key":"2023042013361381700_ref27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12859-017-1511-5","article-title":"A comparison of reference-based algorithms for correcting cell-type heterogeneity in epigenome-wide association studies","volume":"18","author":"Teschendorff","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"2023042013361381700_ref28","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1038\/s41467-020-16919-w","article-title":"Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity","volume":"11","author":"Dahlet","year":"2020","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref29","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1242\/dev.081661","article-title":"Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline","volume":"139","author":"Hackett","year":"2012","journal-title":"Development"},{"key":"2023042013361381700_ref30","doi-asserted-by":"crossref","first-page":"1391807","DOI":"10.1155\/2022\/1391807","article-title":"X-chromosome inactivation and related diseases","volume":"2022","author":"Sun","year":"2022","journal-title":"Genet. Res. (Camb)"},{"key":"2023042013361381700_ref31","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1126\/science.1136352","article-title":"Gene body-specific methylation on the active X chromosome","volume":"315","author":"Hellman","year":"2007","journal-title":"Science"},{"key":"2023042013361381700_ref60","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/21541264.2020.1790990","article-title":"RNA polymerase II-binding aptamers in human ACRO1 satellites disrupt transcription in cis","volume":"11","author":"Boots","year":"2020","journal-title":"Transcription"},{"key":"2023042013361381700_ref61","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/0888-7543(92)90450-7","article-title":"Beta satellite DNA: characterization and localization of two subfamilies from the distal and proximal short arms of the human acrocentric chromosomes","volume":"12","author":"Greig","year":"1992","journal-title":"Genomics"},{"key":"2023042013361381700_ref62","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/0888-7543(95)80039-O","article-title":"D20S16 is a complex interspersed repeated sequence: genetic and physical analysis of the locus","volume":"25","author":"Bowden","year":"1995","journal-title":"Genomics"},{"key":"2023042013361381700_ref63","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ygeno.2007.10.014","article-title":"DA and Xiao-two giant and composite LTR-retrotransposon-like elements identified in the human genome","volume":"91","author":"Ji","year":"2008","journal-title":"Genomics"},{"issue":"485\u2013496","key":"2023042013361381700_ref32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.str.2018.11.012","article-title":"Structure of the UHRF1 tandem tudor domain bound to a methylated non-histone protein, LIG1, reveals rules for binding and regulation","volume":"27","author":"Kori","year":"2019","journal-title":"Structure"},{"key":"2023042013361381700_ref33","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1128\/MCB.24.6.2526-2535.2004","article-title":"Np95 is a histone-binding protein endowed with ubiquitin ligase activity","volume":"24","author":"Citterio","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"2023042013361381700_ref34","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/gtc.12850","article-title":"Chromatin remodeling in replication-uncoupled maintenance DNA methylation and chromosome stability: insights from ICF syndrome studies","volume":"26","author":"Unoki","year":"2021","journal-title":"Genes Cells"},{"key":"2023042013361381700_ref35","doi-asserted-by":"crossref","first-page":"34549","DOI":"10.1074\/jbc.M205189200","article-title":"Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks","volume":"277","author":"Muto","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2023042013361381700_ref36","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1038\/s41467-021-23809-2","article-title":"The epigenetic regulator LSH maintains fork protection and genomic stability via MacroH2A deposition and RAD51 filament formation","volume":"12","author":"Xu","year":"2021","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref37","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1136\/jmedgenet-2017-105190","article-title":"Maternal variants in NLRP and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring","volume":"55","author":"Begemann","year":"2018","journal-title":"J. Med. Genet."},{"key":"2023042013361381700_ref38","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/jhg.2013.51","article-title":"Epigenetic and genetic alterations of the imprinting disorder Beckwith\u2013Wiedemann syndrome and related disorders","volume":"58","author":"Soejima","year":"2013","journal-title":"J. Hum. Genet."},{"key":"2023042013361381700_ref39","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.ecl.2017.01.007","article-title":"Genetics of adrenocortical development and tumors","volume":"46","author":"Lodish","year":"2017","journal-title":"Endocrinol. Metab. Clin. North Am."},{"key":"2023042013361381700_ref40","doi-asserted-by":"crossref","first-page":"12464","DOI":"10.1038\/ncomms12464","article-title":"Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals","volume":"7","author":"Zhao","year":"2016","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref41","doi-asserted-by":"crossref","first-page":"11197","DOI":"10.1038\/ncomms11197","article-title":"Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition","volume":"7","author":"Fang","year":"2016","journal-title":"Nat. Commun."},{"issue":"753\u2013765","key":"2023042013361381700_ref42","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.molcel.2018.09.029","article-title":"A bifunctional role for the UHRF1 UBL domain in the control of hemi-methylated DNA-dependent histone ubiquitylation","volume":"72","author":"DaRosa","year":"2018","journal-title":"Mol. Cell"},{"key":"2023042013361381700_ref43","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.molcel.2018.09.028","article-title":"Critical role of the UBL domain in stimulating the E3 ubiquitin ligase activity of UHRF1 toward chromatin","volume":"72","author":"Foster","year":"2018","journal-title":"Mol. Cell"},{"key":"2023042013361381700_ref44","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1016\/j.jmb.2020.05.006","article-title":"Serine 298 phosphorylation in linker 2 of UHRF1 regulates ligand-binding property of its tandem tudor domain","volume":"432","author":"Kori","year":"2020","journal-title":"J. Mol. Biol."},{"key":"2023042013361381700_ref45","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1038\/s41467-020-17531-8","article-title":"DNA sequence-dependent activity and base flipping mechanisms of DNMT1 regulate genome-wide DNA methylation","volume":"11","author":"Adam","year":"2020","journal-title":"Nat. Commun."},{"key":"2023042013361381700_ref46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007042","article-title":"Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos","volume":"13","author":"Maenohara","year":"2017","journal-title":"PLoS Genet."},{"key":"2023042013361381700_ref47","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1038\/embor.2009.201","article-title":"Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells","volume":"10","author":"Meilinger","year":"2009","journal-title":"EMBO Rep."},{"key":"2023042013361381700_ref48","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12864-016-3392-9","article-title":"Software updates in the Illumina HiSeq platform affect whole-genome bisulfite sequencing","volume":"18","author":"Toh","year":"2017","journal-title":"BMC Genomics"},{"key":"2023042013361381700_ref49","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"2023042013361381700_ref50","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nbt.1754","article-title":"Integrative genomics viewer","volume":"29","author":"Robinson","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"2023042013361381700_ref51","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/bioinformatics\/btt684","article-title":"ChAMP: 450k chip analysis methylation pipeline","volume":"30","author":"Morris","year":"2014","journal-title":"Bioinformatics"},{"key":"2023042013361381700_ref52","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"2023042013361381700_ref53","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/nbt.2647","article-title":"DNA targeting specificity of RNA-guided Cas9 nucleases","volume":"31","author":"Hsu","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2023042013361381700_ref54","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1242\/dev.061416","article-title":"Dynamic stage-specific changes in imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes","volume":"138","author":"Tomizawa","year":"2011","journal-title":"Development"},{"key":"2023042013361381700_ref55","doi-asserted-by":"crossref","first-page":"W170","DOI":"10.1093\/nar\/gkn294","article-title":"QUMA: quantification tool for methylation analysis","volume":"36","author":"Kumaki","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"2023042013361381700_ref56","doi-asserted-by":"crossref","DOI":"10.1063\/1.4952937","article-title":"Software development for analysis of small-angle X-ray scattering data","volume":"1741","author":"Shimizu","year":"2016","journal-title":"AIP Confonference Proceedings"},{"key":"2023042013361381700_ref57","volume-title":"AIP Conference Proceedings","author":"Yonezawa","year":"2019"},{"key":"2023042013361381700_ref58","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nature12070","article-title":"Accurate assessment of mass, models and resolution by small-angle scattering","volume":"496","author":"Rambo","year":"2013","journal-title":"Nature"},{"key":"2023042013361381700_ref59","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1107\/S0021889812007662","article-title":"New developments in the ATSAS program package for small-angle scattering data analysis","volume":"45","author":"Petoukhov","year":"2012","journal-title":"J. Appl. Crystallogr."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddac291\/48533403\/ddac291.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/32\/9\/1439\/50045305\/ddac291.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/32\/9\/1439\/50045305\/ddac291.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T16:51:53Z","timestamp":1682009513000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/32\/9\/1439\/6864905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,2]]},"references-count":63,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,12,2]]},"published-print":{"date-parts":[[2023,4,20]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddac291","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,5,1]]},"published":{"date-parts":[[2022,12,2]]}}}