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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,5,16]]},"abstract":"<jats:p>\n                    In mammals, male and female gonads initially develop from bipotential progenitor cells, which can differentiate into either testicular or ovarian cells. The decision to adopt a testicular or ovarian fate relies on robust genetic forces, i.e., activation of the testis-determining gene\n                    <jats:italic>Sry<\/jats:italic>\n                    , as well as a delicate balance of expression levels for pro-testis and pro-ovary factors. Recently, epigenetic regulation has been found to be a key element in activation of\n                    <jats:italic>Sry<\/jats:italic>\n                    . Nevertheless, the mechanism by which epigenetic regulation controls the expression balance of pro-testis and pro-ovary factors remains unclear. Chromodomain Y-like protein (CDYL) is a reader protein for repressive histone H3 methylation marks. We found that a subpopulation of\n                    <jats:italic>Cdyl<\/jats:italic>\n                    -deficient mice exhibited XY sex reversal. Gene expression analysis revealed that the testis-promoting gene\n                    <jats:italic>Sox9<\/jats:italic>\n                    was downregulated in XY\n                    <jats:italic>Cdyl<\/jats:italic>\n                    -deficient gonads during the sex determination period without affecting\n                    <jats:italic>Sry<\/jats:italic>\n                    expression. Instead, we found that the ovary-promoting gene\n                    <jats:italic>Wnt4<\/jats:italic>\n                    was derepressed in XY\n                    <jats:italic>Cdyl<\/jats:italic>\n                    -deficient gonads prior to and during the sex-determination period.\n                    <jats:italic>Wnt4<\/jats:italic>\n                    heterozygous deficiency restored\n                    <jats:italic>SOX9<\/jats:italic>\n                    expression in\n                    <jats:italic>Cdyl<\/jats:italic>\n                    -deficient XY gonads, indicating that derepressed\n                    <jats:italic>Wnt4<\/jats:italic>\n                    is a cause of the repression of\n                    <jats:italic>Sox9<\/jats:italic>\n                    . We found that CDYL directly bound to the\n                    <jats:italic>Wnt4<\/jats:italic>\n                    promoter and maintained its H3K27me3 levels during the sex-determination period. These findings indicate that CDYL reinforces male gonadal sex determination by repressing the ovary-promoting pathway in mice.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2221499120","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T15:17:50Z","timestamp":1683559070000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":7,"title":["CDYL reinforces male gonadal sex determination through epigenetically repressing\n                    <i>Wnt4<\/i>\n                    transcription in mice"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1795-2115","authenticated-orcid":false,"given":"Naoki","family":"Okashita","sequence":"first","affiliation":[{"name":"Laboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-7392","authenticated-orcid":false,"given":"Ryo","family":"Maeda","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-1120","authenticated-orcid":false,"given":"Makoto","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Laboratory of Epigenome Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.11"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1338"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aas9408"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000499274"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1239864"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007034"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx398"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/31482"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007895"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50058-7"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/7771"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082248899"},{"key":"e_1_3_4_13_2","article-title":"Cdyl deficiency brakes neuronal excitability and nociception through promoting Kcnb1 transcription in peripheral sensory neurons","volume":"9","author":"Sun Z. 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