{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:33:32Z","timestamp":1790696012835,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010152933"],"award-info":[{"award-number":["PJT\u2010152933"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To gain further insight into chromatin\u2010mediated regulation of mammalian sex determination, we analyzed the role of the CHARGE syndrome\u2010associated proteins FAM172A and CHD7. This study is based on our prior discoveries that a subset of corresponding mutant mice display complete male\u2010to\u2010female sex reversal, and that both of these proteins regulate co\u2010transcriptional alternative splicing in neural crest cells. Here, we report that FAM172A and CHD7 are present in the developing gonads when sex determination normally occurs in mice. The interactome of FAM172A in pre\u2010Sertoli cells again suggests a role at the chromatin\u2010spliceosome interface, like in neural crest cells. Accordingly, analysis of\n                    <jats:italic>Fam172a<\/jats:italic>\n                    \u2010mutant pre\u2010Sertoli cells revealed transcriptional and splicing dysregulation of hundreds of genes. Many of these genes are similarly affected in\n                    <jats:italic>Chd7<\/jats:italic>\n                    \u2010mutant pre\u2010Sertoli cells, including several known key regulators of sex determination and subsequent formation of testis cords. Among them, we notably identified\n                    <jats:italic>Sry<\/jats:italic>\n                    as a direct transcriptional target and WNT pathway\u2010associated\n                    <jats:italic>Lef1<\/jats:italic>\n                    and\n                    <jats:italic>Tcf7l2<\/jats:italic>\n                    as direct splicing targets. The identified molecular defects are also associated with the abnormal morphology of seminiferous tubules in mutant postnatal testes. Altogether, our results thus identify FAM172A and CHD7 as new players in the regulation of male sex determination and differentiation in mice, and further highlight the importance of chromatin\u2010mediated regulatory mechanisms in these processes.\n                  <\/jats:p>","DOI":"10.1096\/fj.202100837rr","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T11:12:40Z","timestamp":1644232360000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["CHARGE syndrome\u2010associated proteins FAM172A and CHD7 influence male sex determination and differentiation through transcriptional and alternative splicing mechanisms"],"prefix":"10.1096","volume":"36","author":[{"given":"Catherine","family":"B\u00e9langer","sequence":"first","affiliation":[{"name":"Molecular Genetics of Development Laboratory D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines \u2013 Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Cardinal","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines \u2013 Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Leduc","sequence":"additional","affiliation":[{"name":"Molecular Genetics of Development Laboratory D\u00e9partement des Sciences Biologiques Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al (UQAM)  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Centre d\u2019Excellence en Recherche sur les Maladies Orphelines \u2013 Fondation Courtois (CERMO\u2010FC) Universit\u00e9 du Qu\u00e9bec \u00e0 Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Viger","sequence":"additional","affiliation":[{"name":"Reproduction, Mother and Child Health Centre de recherche en reproduction, d\u00e9veloppement et sant\u00e9 interg\u00e9n\u00e9rationnelle (CRDSI) Centre de recherche du CHU de Qu\u00e9bec\u2010Universit\u00e9 Laval  Quebec City Qu\u00e9bec Canada"},{"name":"Department of Obstetrics, Gynecology, and Reproduction Faculty of Medicine Universit\u00e9 Laval  Quebec City Qu\u00e9bec 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