{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:01:36Z","timestamp":1790845296128,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5 R01 GM59152"],"award-info":[{"award-number":["5 R01 GM59152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5 R01 GM127379"],"award-info":[{"award-number":["5 R01 GM127379"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Minnesota Medical School"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sex determination in mammals hinges on a cell fate decision in the fetal bipotential gonad between formation of male Sertoli cells or female granulosa cells. While this decision normally is permanent, loss of key cell fate regulators such as the transcription factors Dmrt1 and Foxl2 can cause postnatal transdifferentiation from Sertoli to granulosa-like (Dmrt1) or vice versa (Foxl2). Here, we examine the mechanism of male-to-female transdifferentiation in mice carrying either a null mutation of Dmrt1 or a point mutation, R111G, that alters the DNA-binding motif and causes human XY gonadal dysgenesis and sex reversal. We first define genes misexpressed during transdifferentiation and then show that female transcriptional regulators driving transdifferentiation in the mutant XY gonad (ESR2, LRH1, FOXL2) bind chromatin sites related to those normally bound in the XX ovary. We next define gene expression changes and abnormal chromatin compartments at the onset of transdifferentiation that may help destabilize cell fate and initiate the transdifferentiation process. We model the R111G mutation in mice and show that it causes dominant gonadal dysgenesis, analogous to its human phenotype but less severe. We show that R111G partially feminizes the testicular transcriptome and causes dominant disruption of DMRT1 binding specificity in vivo. These data help illuminate how transdifferentiation occurs when sexual cell fate maintenance is disrupted and identify chromatin sites and transcripts that may play key roles in the transdifferentiation process.<\/jats:p>","DOI":"10.1093\/g3journal\/jkac267","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T13:48:45Z","timestamp":1665064125000},"source":"Crossref","is-referenced-by-count":10,"title":["Genomics of sexual cell fate transdifferentiation in the mouse gonad"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9520-1213","authenticated-orcid":false,"given":"Mark W","family":"Murphy","sequence":"first","affiliation":[{"name":"Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota , Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-1930","authenticated-orcid":false,"given":"Micah D","family":"Gearhart","sequence":"additional","affiliation":[{"name":"Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota , Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-5419","authenticated-orcid":false,"given":"Andrew","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota , Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1459-8897","authenticated-orcid":false,"given":"Vivian J","family":"Bardwell","sequence":"additional","affiliation":[{"name":"Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota , Minneapolis, MN 55455, USA"},{"name":"University of Minnesota Masonic Cancer Center , Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7708-9531","authenticated-orcid":false,"given":"David","family":"Zarkower","sequence":"additional","affiliation":[{"name":"Developmental Biology Center and Department of Genetics, Cell Biology, and Development, University of Minnesota , Minneapolis, MN 55455, USA"},{"name":"University of Minnesota Masonic Cancer Center , Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"issue":"2","key":"2022120108101689600_jkac267-B1","doi-asserted-by":"crossref","first-page":"e1010088","DOI":"10.1371\/journal.pgen.1010088","article-title":"Lrh1\u00a0can help reprogram sexual cell fate and is required for Sertoli cell 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