{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:02:31Z","timestamp":1790928151323,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["ISF_710_2020"],"award-info":[{"award-number":["ISF_710_2020"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["101039928"],"award-info":[{"award-number":["101039928"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020806","name":"ANR","doi-asserted-by":"publisher","award":["ANR-21-CE14-0061-01"],"award-info":[{"award-number":["ANR-21-CE14-0061-01"]}],"id":[{"id":"10.13039\/100020806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Male development in mammals depends on the activity of the two SOX gene: Sry and Sox9, in the embryonic testis. As deletion of Enhancer 13 (Enh13) of the Sox9 gene results in XY male-to-female sex reversal, we explored the critical elements necessary for its function and hence, for testis and male development. Here, we demonstrate that while microdeletions of individual transcription factor binding sites (TFBS) in Enh13 lead to normal testicular development, combined microdeletions of just two SRY\/SOX binding motifs can alone fully abolish Enh13 activity leading to XY male-to-female sex reversal. This suggests that for proper male development to occur, these few nucleotides of non-coding DNA must be intact. Interestingly, we show that depending on the nature of these TFBS mutations, dramatically different phenotypic outcomes can occur, providing a molecular explanation for the distinct clinical outcomes observed in patients harboring different variants in the same enhancer.<\/jats:p>","DOI":"10.1093\/nar\/gkae178","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T05:35:37Z","timestamp":1710826537000},"page":"5514-5528","source":"Crossref","is-referenced-by-count":17,"title":["Two redundant transcription factor binding sites in a single enhancer are essential for mammalian sex determination"],"prefix":"10.1093","volume":"52","author":[{"given":"Meshi","family":"Ridnik","sequence":"first","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisheva","family":"Abberbock","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Alipov","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelly Ziv","family":"Lhermann","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoham","family":"Kaufman","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maor","family":"Lubman","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Poulat","sequence":"additional","affiliation":[{"name":"Group \u201cDevelopment and Pathology of the Gonad\u201d. Department of Genetics, Cell Biology and Development, Institute of Human Genetics, CNRS-University of Montpellier UMR9002 , Montpellier , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3377-8324","authenticated-orcid":false,"given":"Nitzan","family":"Gonen","sequence":"additional","affiliation":[{"name":"The Mina and Everard Goodman Faculty of Life Sciences and the Institute of Nanotechnology and Advanced Materials, Bar-Ilan University , Ramat Gan\u00a0 5290002 , Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"2024060923570140500_B1","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.molmed.2021.07.012","article-title":"Enhancers in disease: molecular basis and emerging treatment strategies","volume":"27","author":"Claringbould","year":"2021","journal-title":"Trends Mol. Med."},{"key":"2024060923570140500_B2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13072-015-0050-4","article-title":"Making sense of GWAS: using epigenomics and genome engineering to understand the functional relevance of SNPs in non-coding regions of the human genome","volume":"8","author":"Tak","year":"2015","journal-title":"Epigenetics Chromatin"},{"key":"2024060923570140500_B3","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"Maurano","year":"2012","journal-title":"Science"},{"key":"2024060923570140500_B4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/cge.12932","article-title":"Anomalies in human sex determination provide unique insights into the complex genetic interactions of early gonad development","volume":"91","author":"Bashamboo","year":"2017","journal-title":"Clin. Genet."},{"key":"2024060923570140500_B5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1159\/000481896","article-title":"The role of copy number variants in disorders of sex development","volume":"12","author":"Croft","year":"2018","journal-title":"Sex. Dev."},{"key":"2024060923570140500_B6","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41576-021-00365-5","article-title":"Towards improved genetic diagnosis of human differences of sex development","volume":"22","author":"Delot","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"2024060923570140500_B7","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.jpurol.2006.03.004","article-title":"Consensus statement on management of intersex disorders","volume":"2","author":"LWPES1\/ESPE2 Consensus Group","year":"2006","journal-title":"J. Pediatr. Urol."},{"key":"2024060923570140500_B8","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.gde.2015.03.003","article-title":"Cell fate commitment during mammalian sex determination","volume":"32","author":"Lin","year":"2015","journal-title":"Curr. Opin. Genet. Dev."},{"key":"2024060923570140500_B9","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/bs.ctdb.2019.01.002","article-title":"Characterizing the bipotential mammalian gonad","volume":"134","author":"Nef","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"2024060923570140500_B10","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1210\/er.2018-00010","article-title":"At the crossroads of fate-somatic cell lineage specification in the fetal gonad","volume":"39","author":"Rotgers","year":"2018","journal-title":"Endocr. Rev."},{"key":"2024060923570140500_B11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00009.2006","article-title":"Sex determination and gonadal development in mammals","volume":"87","author":"Wilhelm","year":"2007","journal-title":"Physiol. Rev."},{"key":"2024060923570140500_B12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/351117a0","article-title":"Male development of chromosomally female mice transgenic for Sry","volume":"351","author":"Koopman","year":"1991","journal-title":"Nature"},{"key":"2024060923570140500_B13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/346240a0","article-title":"A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif","volume":"346","author":"Sinclair","year":"1990","journal-title":"Nature"},{"key":"2024060923570140500_B14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/bs.ctdb.2019.01.004","article-title":"The regulation of Sox9 expression in the gonad","volume":"134","author":"Gonen","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"2024060923570140500_B15","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1126\/science.aas9408","article-title":"Sex reversal following deletion of a single distal enhancer of Sox9","volume":"360","author":"Gonen","year":"2018","journal-title":"Science"},{"key":"2024060923570140500_B16","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ydbio.2004.07.011","article-title":"SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors","volume":"274","author":"Sekido","year":"2004","journal-title":"Dev. Biol."},{"key":"2024060923570140500_B17","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/nature06944","article-title":"Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer","volume":"453","author":"Sekido","year":"2008","journal-title":"Nature"},{"key":"2024060923570140500_B18","doi-asserted-by":"crossref","first-page":"7191","DOI":"10.1093\/nar\/gkx328","article-title":"In mammalian foetal testes, SOX9 regulates expression of its target genes by binding to genomic regions with conserved signatures","volume":"45","author":"Rahmoun","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2024060923570140500_B19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1095\/biolreprod.105.045930","article-title":"Homozygous inactivation of Sox9 causes complete XY sex reversal in mice","volume":"74","author":"Barrionuevo","year":"2006","journal-title":"Biol. Reprod."},{"key":"2024060923570140500_B20","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/372525a0","article-title":"Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene","volume":"372","author":"Foster","year":"1994","journal-title":"Nature"},{"key":"2024060923570140500_B21","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/0092-8674(94)90041-8","article-title":"Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9","volume":"79","author":"Wagner","year":"1994","journal-title":"Cell"},{"key":"2024060923570140500_B22","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1242\/dev.01087","article-title":"Functional analysis of Sox8 and Sox9 during sex determination in the mouse","volume":"131","author":"Chaboissier","year":"2004","journal-title":"Development"},{"key":"2024060923570140500_B23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/(SICI)1096-8628(19991203)87:4<349::AID-AJMG13>3.0.CO;2-N","article-title":"Autosomal XX sex reversal caused by duplication of SOX9","volume":"87","author":"Huang","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"2024060923570140500_B24","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/90046","article-title":"Sox9 induces testis development in XX transgenic mice","volume":"28","author":"Vidal","year":"2001","journal-title":"Nat. Genet."},{"key":"2024060923570140500_B25","doi-asserted-by":"crossref","first-page":"5319","DOI":"10.1038\/s41467-018-07784-9","article-title":"Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9","volume":"9","author":"Croft","year":"2018","journal-title":"Nat. Commun."},{"key":"2024060923570140500_B26","doi-asserted-by":"crossref","first-page":"17514","DOI":"10.1038\/s41598-018-35746-0","article-title":"Mapping of a responsible region for sex reversal upstream of Sox9 by production of mice with serial deletion in a genomic locus","volume":"8","author":"Ogawa","year":"2018","journal-title":"Sci. Rep."},{"key":"2024060923570140500_B27","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1002\/ajmg.a.63367","article-title":"The smallest likely pathogenic duplication of a SOX9 enhancer identified to date in a family with 46,XX testicular differences of sex development","volume":"191","author":"Sajan","year":"2023","journal-title":"Am. J. Med. Genet. A."},{"key":"2024060923570140500_B28","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/ng0696-230","article-title":"Sex reversal by loss of the C-terminal transactivation domain of human SOX9","volume":"13","author":"Sudbeck","year":"1996","journal-title":"Nat. Genet."},{"key":"2024060923570140500_B29","doi-asserted-by":"crossref","first-page":"38625","DOI":"10.1074\/jbc.M504127200","article-title":"NHERF2\/SIP-1 interacts with mouse SRY via a different mechanism than human SRY","volume":"280","author":"Thevenet","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2024060923570140500_B30","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1128\/MCB.18.11.6653","article-title":"Direct interaction of SRY-related protein SOX9 and steroidogenic factor 1 regulates transcription of the human anti-Mullerian hormone gene","volume":"18","author":"De\u00a0Santa\u00a0Barbara","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"2024060923570140500_B31","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ab.2009.09.043","article-title":"Factors modulating expression of Renilla luciferase from control plasmids used in luciferase reporter gene assays","volume":"396","author":"Shifera","year":"2010","journal-title":"Anal. Biochem."},{"key":"2024060923570140500_B32","doi-asserted-by":"crossref","first-page":"5917","DOI":"10.1074\/jbc.M412806200","article-title":"The transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development","volume":"280","author":"Wilson","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2024060923570140500_B33","doi-asserted-by":"crossref","first-page":"dev171736","DOI":"10.1242\/dev.171736","article-title":"The regulatory landscapes of developmental genes","volume":"147","author":"Bolt","year":"2020","journal-title":"Development"},{"key":"2024060923570140500_B34","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.cell.2017.12.017","article-title":"Ultraconserved enhancers are required for normal development","volume":"172","author":"Dickel","year":"2018","journal-title":"Cell"},{"key":"2024060923570140500_B35","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/nature25461","article-title":"Enhancer redundancy provides phenotypic robustness in mammalian development","volume":"554","author":"Osterwalder","year":"2018","journal-title":"Nature"},{"key":"2024060923570140500_B36","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/ng.3939","article-title":"Composition and dosage of a multipartite enhancer cluster control developmental expression of Ihh (Indian hedgehog)","volume":"49","author":"Will","year":"2017","journal-title":"Nat. Genet."},{"key":"2024060923570140500_B37","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/nar\/27.5.1359","article-title":"The DNA-binding specificity of SOX9 and other SOX proteins","volume":"27","author":"Mertin","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"2024060923570140500_B38","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.celrep.2014.06.055","article-title":"The sex-determining factors SRY and SOX9 regulate similar target genes and promote testis cord formation during testicular differentiation","volume":"8","author":"Li","year":"2014","journal-title":"Cell Rep."},{"key":"2024060923570140500_B39","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<111::AID-GENE40>3.0.CO;2-5","article-title":"Related function of mouse SOX3, SOX9, and SRY HMG domains assayed by male sex determination","volume":"28","author":"Bergstrom","year":"2000","journal-title":"Genesis"},{"key":"2024060923570140500_B40","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000524453","article-title":"SOX genes and their role in disorders of sex development","volume":"16","author":"Sreenivasan","year":"2022","journal-title":"Sex. Dev."},{"key":"2024060923570140500_B41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/hmg\/ddac184","article-title":"SOX9 and SRY binding sites on mouse mXYSRa\/Enh13 enhancer redundantly regulate Sox9 expression to varying degrees","volume":"32","author":"Ogawa","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"2024060923570140500_B42","doi-asserted-by":"crossref","first-page":"eabm0972","DOI":"10.1126\/sciadv.abm0972","article-title":"Origin, specification and differentiation of a rare supporting-like lineage in the developing mouse gonad","volume":"8","author":"Mayere","year":"2022","journal-title":"Sci. Adv."},{"key":"2024060923570140500_B43","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1016\/j.celrep.2019.02.069","article-title":"Dissecting cell lineage specification and sex fate determination in gonadal somatic cells using single-cell transcriptomics","volume":"26","author":"Stevant","year":"2019","journal-title":"Cell Rep."},{"key":"2024060923570140500_B44","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.celrep.2018.01.043","article-title":"Deciphering cell lineage specification during male sex determination with single-cell RNA sequencing","volume":"22","author":"Stevant","year":"2018","journal-title":"Cell Rep."},{"key":"2024060923570140500_B45","doi-asserted-by":"crossref","first-page":"13680","DOI":"10.1073\/pnas.1921676117","article-title":"Testis formation in XX individuals resulting from novel pathogenic variants in Wilms' tumor 1 (WT1) gene","volume":"117","author":"Eozenou","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2024060923570140500_B46","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/0092-8674(93)90515-R","article-title":"WT-1 is required for early kidney development","volume":"74","author":"Kreidberg","year":"1993","journal-title":"Cell"},{"key":"2024060923570140500_B47","doi-asserted-by":"crossref","first-page":"R196","DOI":"10.1093\/hmg\/ddl196","article-title":"The many facets of the Wilms' tumour gene, WT1","author":"Hohenstein","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"2024060923570140500_B48","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.mce.2015.01.009","article-title":"Steroidogenic organ development and homeostasis: A WT1-centric view","volume":"408","author":"Bandiera","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"2024060923570140500_B49","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1126\/science.add8831","article-title":"The -KTS splice variant of WT1 is essential for ovarian determination in mice","volume":"382","author":"Gregoire","year":"2023","journal-title":"Science"},{"key":"2024060923570140500_B50","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0092-8674(01)00453-6","article-title":"Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation","volume":"106","author":"Hammes","year":"2001","journal-title":"Cell"},{"key":"2024060923570140500_B51","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/nar\/28.16.3047","article-title":"The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences","volume":"28","author":"Peirano","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"2024060923570140500_B52","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrg.2017.116","article-title":"Paediatric genomics: diagnosing rare disease in children","volume":"19","author":"Wright","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"2024060923570140500_B53","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0092-8674(00)81527-5","article-title":"Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development","volume":"99","author":"Arango","year":"1999","journal-title":"Cell"},{"key":"2024060923570140500_B54","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1093\/nar\/gkf690","article-title":"Cooperative binding of Sox10 to DNA: requirements and consequences","volume":"30","author":"Schlierf","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"2024060923570140500_B55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.semcdb.2016.08.005","article-title":"Molecular basis for the genome engagement by Sox proteins","volume":"63","author":"Hou","year":"2017","journal-title":"Semin. Cell Dev. Biol."},{"key":"2024060923570140500_B56","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1093\/hmg\/ddg182","article-title":"Dimerization of SOX9 is required for chondrogenesis, but not for sex determination","volume":"12","author":"Bernard","year":"2003","journal-title":"Hum. Mol. Genet."},{"key":"2024060923570140500_B57","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1126\/science.aau0320","article-title":"Developmental enhancers and chromosome topology","volume":"361","author":"Furlong","year":"2018","journal-title":"Science"},{"key":"2024060923570140500_B58","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jmb.2019.10.014","article-title":"Higher-order chromosomal structures mediate genome function","volume":"432","author":"Jerkovic","year":"2020","journal-title":"J. Mol. Biol."},{"key":"2024060923570140500_B59","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.cell.2016.09.018","article-title":"Ever-changing landscapes: transcriptional enhancers in development and evolution","volume":"167","author":"Long","year":"2016","journal-title":"Cell"},{"key":"2024060923570140500_B60","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/0092-8674(95)90136-1","article-title":"Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome","volume":"83","author":"Thanos","year":"1995","journal-title":"Cell"},{"key":"2024060923570140500_B61","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41586-023-06922-8","article-title":"Affinity-optimizing variants within the ZRS enhancer disrupt limb development","volume":"626","author":"Lim","year":"2024","journal-title":"Nature"},{"key":"2024060923570140500_B62","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.cell.2014.11.041","article-title":"Low affinity binding site clusters confer hox specificity and regulatory robustness","volume":"160","author":"Crocker","year":"2015","journal-title":"Cell"},{"key":"2024060923570140500_B63","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1126\/science.aac6948","article-title":"Suboptimization of developmental enhancers","volume":"350","author":"Farley","year":"2015","journal-title":"Science"},{"key":"2024060923570140500_B64","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1242\/dev.029587","article-title":"A critical time window of Sry action in gonadal sex determination in mice","volume":"136","author":"Hiramatsu","year":"2009","journal-title":"Development"},{"key":"2024060923570140500_B65","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0070-2153(08)00405-5","article-title":"Sexual development of the soma in the mouse","volume":"83","author":"Maatouk","year":"2008","journal-title":"Curr. Top. Dev. Biol."},{"key":"2024060923570140500_B66","doi-asserted-by":"crossref","first-page":"6698","DOI":"10.1073\/pnas.111092198","article-title":"Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization","volume":"98","author":"Bi","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2024060923570140500_B67","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1093\/hmg\/ddaa259","article-title":"Heterozygous deletion of Sox9 in mouse mimics the gonadal sex reversal phenotype associated with campomelic dysplasia in humans","volume":"29","author":"Bagheri-Fam","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"2024060923570140500_B68","doi-asserted-by":"crossref","first-page":"e1006520","DOI":"10.1371\/journal.pgen.1006520","article-title":"Normal levels of Sox9 expression in the developing mouse testis depend on the TES\/TESCO enhancer, but this does not act alone","volume":"13","author":"Gonen","year":"2017","journal-title":"PLoS Genet."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/52\/10\/5514\/58172641\/gkae178.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nar\/article-pdf\/52\/10\/5514\/58172641\/gkae178.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T23:57:47Z","timestamp":1717977467000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/52\/10\/5514\/7631399"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":68,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,3,18]]},"published-print":{"date-parts":[[2024,6,10]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkae178","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,6,10]]},"published":{"date-parts":[[2024,3,18]]}}}