{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:50:45Z","timestamp":1790909445365,"version":"4.1.0"},"reference-count":65,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T00:00:00Z","timestamp":1543363200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM110092"],"award-info":[{"award-number":["R01GM110092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Pericentromeric satellite repeats are enriched in 5-methylcytosine (5mC). Loss of 5mC at these sequences is common in cancer and is a hallmark of Immunodeficiency, Centromere and Facial abnormalities (ICF) syndrome. While the general importance of 5mC is well-established, the specific functions of 5mC at pericentromeres are less clear. To address this deficiency, we generated a viable animal model of pericentromeric hypomethylation through mutation of the ICF-gene ZBTB24. Deletion of zebrafish zbtb24 caused a progressive loss of 5mC at pericentromeres and ICF-like phenotypes. Hypomethylation of these repeats triggered derepression of pericentromeric transcripts and activation of an interferon-based innate immune response. Injection of pericentromeric RNA is sufficient to elicit this response in wild-type embryos, and mutation of the MDA5-MAVS dsRNA-sensing machinery blocks the response in mutants. These findings identify activation of the innate immune system as an early consequence of pericentromeric hypomethylation, implicating derepression of pericentromeric transcripts as a trigger of autoimmunity.<\/jats:p>\n                  <jats:p>Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (&lt;xref ref-type=\"decision-letter\" rid=\"SA1\"&gt;see decision letter&lt;\/xref&gt;).<\/jats:p>","DOI":"10.7554\/elife.39658","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T10:00:11Z","timestamp":1543399211000},"source":"Crossref","is-referenced-by-count":50,"title":["Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-5531","authenticated-orcid":true,"given":"Srivarsha","family":"Rajshekar","sequence":"first","affiliation":[{"name":"Program in Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, United States"},{"name":"Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States"},{"name":"Institute of Bioinformatics, University of Georgia, Athens, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige K","family":"Arnold","sequence":"additional","affiliation":[{"name":"Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-9112","authenticated-orcid":true,"given":"Sara G","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Bioinformatics, University of Georgia, Athens, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa V","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Georgia, Georgia, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Pharmacogenomics, Washington University in St. Louis School of Medicine, Missouri, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5003-6958","authenticated-orcid":true,"given":"Mary","family":"Goll","sequence":"additional","affiliation":[{"name":"Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States"},{"name":"Department of Genetics, University of Georgia, Georgia, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2018,11,28]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"R106","DOI":"10.1186\/gb-2010-11-10-r106","article-title":"Differential expression analysis for sequence count data","volume":"11","author":"Anders","year":"2010","journal-title":"Genome Biology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ydbio.2009.07.017","article-title":"Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration","volume":"334","author":"Anderson","year":"2009","journal-title":"Developmental Biology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nature11537","article-title":"In vivo genome editing using a high-efficiency TALEN system","volume":"491","author":"Bedell","year":"2012","journal-title":"Nature"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"R92","DOI":"10.1186\/gb-2012-13-10-r92","article-title":"Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling","volume":"13","author":"Boyle","year":"2012","journal-title":"Genome Biology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1242\/dev.134809","article-title":"Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes","volume":"143","author":"Burger","year":"2016","journal-title":"Development"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"e82","DOI":"10.1093\/nar\/gkr218","article-title":"Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting","volume":"39","author":"Cermak","year":"2011","journal-title":"Nucleic Acids Research"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1053\/j.seminoncol.2014.02.002","article-title":"Interferons and their stimulated genes in the tumor microenvironment","volume":"41","author":"Cheon","year":"2014","journal-title":"Seminars in Oncology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"2925","DOI":"10.1242\/dev.147629","article-title":"Loss of DNA methylation in zebrafish embryos activates retrotransposons to trigger antiviral signaling","volume":"144","author":"Chernyavskaya","year":"2017","journal-title":"Development"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1016\/j.cell.2015.07.011","article-title":"Inhibiting dna methylation causes an interferon response in cancer via dsrna including endogenous retroviruses","volume":"162","author":"Chiappinelli","year":"2015","journal-title":"Cell"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1146\/annurev-immunol-051116-052331","article-title":"Intracellular nucleic acid detection in autoimmunity","volume":"35","author":"Crowl","year":"2017","journal-title":"Annual Review of Immunology"},{"key":"bib13","doi-asserted-by":"publisher","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":"de Greef","year":"2011","journal-title":"The American Journal of Human Genetics"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"W117","DOI":"10.1093\/nar\/gks608","article-title":"TAL Effector-Nucleotide Targeter (TALE-NT) 2.0: tools for TAL effector design and target prediction","volume":"40","author":"Doyle","year":"2012","journal-title":"Nucleic Acids Research"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/S1521-6616(03)00201-8","article-title":"The ICF syndrome, a DNA methyltransferase 3B deficiency and immunodeficiency disease","volume":"109","author":"Ehrlich","year":"2003","journal-title":"Clinical Immunology"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1080\/08916930802024202","article-title":"ICF, an immunodeficiency syndrome: DNA methyltransferase 3B involvement, chromosome anomalies, and gene dysregulation","volume":"41","author":"Ehrlich","year":"2008","journal-title":"Autoimmunity"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1038\/nmeth.2722","article-title":"Systematic evaluation of spliced alignment programs for RNA-seq data","volume":"10","author":"Engstr\u00f6m","year":"2013","journal-title":"Nature Methods"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1159\/000106440","article-title":"Human chromosome 1 satellite 3 DNA is decondensed, demethylated and transcribed in senescent cells and in A431 epithelial carcinoma cells","volume":"118","author":"Enukashvily","year":"2007","journal-title":"Cytogenetic and Genome Research"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1038\/sj.onc.1210642","article-title":"Loss of pericentromeric DNA methylation pattern in human glioblastoma is associated with altered DNA methyltransferases expression and involves the stem cell compartment","volume":"27","author":"Fanelli","year":"2008","journal-title":"Oncogene"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"e98186","DOI":"10.1371\/journal.pone.0098186","article-title":"Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs","volume":"9","author":"Gagnon","year":"2014","journal-title":"PLOS ONE"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"e52246","DOI":"10.3791\/52246","article-title":"Enhanced reduced representation bisulfite sequencing for assessment of DNA methylation at base pair resolution","author":"Garrett-Bakelman","year":"2015","journal-title":"Journal of Visualized Experiments"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/S0304-4165(01)00129-5","article-title":"Lsh, a SNF2 family member, is required for normal murine development","volume":"1526","author":"Geiman","year":"2001","journal-title":"Biochimica Et Biophysica Acta (BBA) - General Subjects"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1146\/annurev.biochem.74.010904.153721","article-title":"Eukaryotic cytosine methyltransferases","volume":"74","author":"Goll","year":"2005","journal-title":"Annual Review of Biochemistry"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: scanning for occurrences of a given motif","volume":"27","author":"Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.immuni.2015.01.012","article-title":"DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity","volume":"42","author":"H\u00e4rtlova","year":"2015","journal-title":"Immunity"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12977-015-0138-8","article-title":"Selective expression of sense and antisense transcripts of the sushi-ichi-related retrotransposon--derived family during mouse placentogenesis","volume":"12","author":"Henke","year":"2015","journal-title":"Retrovirology"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"13904","DOI":"10.1073\/pnas.1308335110","article-title":"Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system","volume":"110","author":"Jao","year":"2013","journal-title":"PNAS"},{"key":"bib29","doi-asserted-by":"publisher","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":"PNAS"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biology"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"W272","DOI":"10.1093\/nar\/gkw398","article-title":"CHOPCHOP v2: a web tool for the next generation of CRISPR genome engineering","volume":"44","author":"Labun","year":"2016","journal-title":"Nucleic Acids Research"},{"key":"bib32","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1242\/dev.122.10.3195","article-title":"De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells","volume":"122","author":"Lei","year":"1996","journal-title":"Development"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"E89","DOI":"10.1073\/pnas.1216922110","article-title":"p53 cooperates with DNA methylation and a suicidal interferon response to maintain epigenetic silencing of repeats and noncoding RNAs","volume":"110","author":"Leonova","year":"2013","journal-title":"PNAS"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1016\/j.celrep.2015.07.025","article-title":"Overlapping requirements for tet2 and tet3 in normal development and hematopoietic stem cell emergence","volume":"12","author":"Li","year":"2015","journal-title":"Cell Reports"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.15252\/embj.201488726","article-title":"Cytosolic RNA:DNA hybrids activate the cGAS-STING axis","volume":"33","author":"Mankan","year":"2014","journal-title":"The EMBO Journal"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1006\/dbio.1998.9105","article-title":"A role for DNA methylation in gastrulation and somite patterning","volume":"206","author":"Martin","year":"1999","journal-title":"Developmental Biology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1097\/01.ju.0000141577.98902.49","article-title":"DNA hypomethylation on pericentromeric satellite regions significantly correlates with loss of heterozygosity on chromosome 9 in urothelial carcinomas","volume":"173","author":"Nakagawa","year":"2005","journal-title":"The Journal of Urology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1002\/(SICI)1097-0215(19980911)77:6<833::AID-IJC6>3.0.CO;2-V","article-title":"Hypomethylation of pericentromeric DNA in breast adenocarcinomas","volume":"77","author":"Narayan","year":"1998","journal-title":"International Journal of Cancer"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"2975","DOI":"10.1002\/dvdy.22113","article-title":"Normal table of postembryonic zebrafish development: staging by externally visible anatomy of the living fish","volume":"238","author":"Parichy","year":"2009","journal-title":"Developmental Dynamics"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1093\/bioinformatics\/btw026","article-title":"Differential methylation analysis for BS-seq data under general experimental design","volume":"32","author":"Park","year":"2016","journal-title":"Bioinformatics"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1023\/A:1009271017998","article-title":"Localization of repetitive DNAs to zebrafish (Danio rerio) chromosomes by fluorescence in situ hybridization (FISH)","volume":"8","author":"Phillips","year":"2000","journal-title":"Chromosome Research"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S0165-4608(98)00143-5","article-title":"Frequent hypomethylation in Wilms tumors of pericentromeric DNA in chromosomes 1 and 16","volume":"109","author":"Qu","year":"1999","journal-title":"Cancer Genetics and Cytogenetics"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"7077","DOI":"10.1128\/MCB.00312-06","article-title":"Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development","volume":"26","author":"Rai","year":"2006","journal-title":"Molecular and Cellular Biology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.cell.2015.07.056","article-title":"Dna-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts","volume":"162","author":"Roulois","year":"2015","journal-title":"Cell"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1146\/annurev-immunol-032713-120231","article-title":"Interferon-stimulated genes: a complex web of host defenses","volume":"32","author":"Schneider","year":"2014","journal-title":"Annual Review of Immunology"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nrg3354","article-title":"DNA methylation: roles in mammalian development","volume":"14","author":"Smith","year":"2013","journal-title":"Nature Reviews Genetics"},{"key":"bib47","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1101\/gad.14.3.313","article-title":"Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos","volume":"14","author":"Stancheva","year":"2000","journal-title":"Genes & development"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/S0531-5565(02)00061-X","article-title":"Demethylation of classical satellite 2 and 3 DNA with chromosomal instability in senescent human fibroblasts","volume":"37","author":"Suzuki","year":"2002","journal-title":"Experimental Gerontology"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/nrg2341","article-title":"DNA methylation landscapes: provocative insights from epigenomics","volume":"9","author":"Suzuki","year":"2008","journal-title":"Nature Reviews Genetics"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"15154","DOI":"10.1073\/pnas.1517584112","article-title":"Distinguishing the immunostimulatory properties of noncoding RNAs expressed in cancer cells","volume":"112","author":"Tanne","year":"2015","journal-title":"PNAS"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"5626","DOI":"10.1073\/pnas.1017000108","article-title":"Lsh, chromatin remodeling family member, modulates genome-wide cytosine methylation patterns at nonrepeat sequences","volume":"108","author":"Tao","year":"2011","journal-title":"PNAS"},{"key":"bib52","doi-asserted-by":"publisher","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":"Nature Communications"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"10034","DOI":"10.1093\/nar\/gky682","article-title":"ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation","author":"Thompson","year":"2018","journal-title":"Nucleic Acids Research"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1126\/science.1200801","article-title":"Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers","volume":"331","author":"Ting","year":"2011","journal-title":"Science"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/S1074-7613(04)00084-6","article-title":"The use of zebrafish to understand immunity","volume":"20","author":"Trede","year":"2004","journal-title":"Immunity"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/S0002-9440(10)64246-0","article-title":"Correlation of DNA hypomethylation at pericentromeric heterochromatin regions of chromosomes 16 and 1 with histological features and chromosomal abnormalities of human breast carcinomas","volume":"161","author":"Tsuda","year":"2002","journal-title":"The American Journal of Pathology"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1159\/000015590","article-title":"DNA hypomethylation and unusual chromosome instability in cell lines from ICF syndrome patients","volume":"89","author":"Tuck-Muller","year":"2000","journal-title":"Cytogenetic and Genome Research"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1242\/dev.02293","article-title":"Roles for Dnmt3b in mammalian development: a mouse model for the ICF syndrome","volume":"133","author":"Ueda","year":"2006","journal-title":"Development"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1242\/dmm.010843","article-title":"Functional analysis of a zebrafish myd88 mutant identifies key transcriptional components of the innate immune system","volume":"6","author":"van der Vaart","year":"2013","journal-title":"Disease Models & Mechanisms"},{"key":"bib60","doi-asserted-by":"publisher","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":"Human Molecular Genetics"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s13023-014-0116-6","article-title":"Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2)","volume":"9","author":"von Bernuth","year":"2014","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"6823","DOI":"10.1093\/nar\/gki987","article-title":"Analysis of repetitive element DNA methylation by MethyLight","volume":"33","author":"Weisenberger","year":"2005","journal-title":"Nucleic Acids Research"},{"key":"bib63","doi-asserted-by":"publisher","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":"Human Molecular Genetics"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/1471-2105-10-232","article-title":"BSMAP: whole genome bisulfite sequence MAPping program","volume":"10","author":"Xi","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"bib65","doi-asserted-by":"publisher","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"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/39658\/elife-39658-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/39658\/elife-39658-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/39658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:00:33Z","timestamp":1697058033000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/39658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,28]]},"references-count":65,"alternative-id":["10.7554\/eLife.39658"],"URL":"https:\/\/doi.org\/10.7554\/elife.39658","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"uri","id":"https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE116360","asserted-by":"subject"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/396671","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.39658.033","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.39658.032","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,28]]},"article-number":"e39658"}}