{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:52:02Z","timestamp":1789044722340,"version":"build-2803163510"},"posted":{"date-parts":[[2024,10,27]]},"group-title":"Genetics","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,27]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Conventionally, Y-linked\n                  <jats:italic>Sry<\/jats:italic>\n                  is thought to drive sex differences by triggering differential hormone production. Ancestral X-Y gene pairs, however, are hypothesized to drive hormone-independent sex differences. Here, we show that the X-Y gene pair\n                  <jats:italic>Kdm5c<\/jats:italic>\n                  -\n                  <jats:italic>Kdm5d<\/jats:italic>\n                  regulates sex-biased gene expression in pluripotent mouse embryonic stem cells (ESCs). Wild-type (WT) XX female ESCs exhibit &gt;2-fold higher expression of 409 genes relative to WT XY male ESCs. Conversely, WT XY male ESCs exhibit &gt;2-fold higher expression of 126 genes compared to WT XX female ESCs. Loss of\n                  <jats:italic>Kdm5c<\/jats:italic>\n                  in female ESCs downregulates female-biased genes. In contrast, loss of either\n                  <jats:italic>Kdm5c<\/jats:italic>\n                  or\n                  <jats:italic>Kdm5d<\/jats:italic>\n                  in male ESCs upregulates female-biased genes and downregulates male-biased genes, effectively neutralizing sex-biased gene expression. KDM5C promotes the expression of\n                  <jats:italic>Kdm5d<\/jats:italic>\n                  and several other Y-linked genes in male ESCs. Moreover, ectopic\n                  <jats:italic>Kdm5d<\/jats:italic>\n                  expression in female ESCs is sufficient to drive male-biased gene expression. These results establish\n                  <jats:italic>Kdm5c<\/jats:italic>\n                  -\n                  <jats:italic>Kdm5d<\/jats:italic>\n                  as critical regulators of sex-biased gene expression.\n                <\/jats:p>","DOI":"10.1101\/2024.10.24.620066","type":"posted-content","created":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T06:15:14Z","timestamp":1730009714000},"source":"Crossref","is-referenced-by-count":2,"title":["Regulation of Sex-biased Gene Expression by the Ancestral X-Y Chromosomal Gene Pair\n                  <i>Kdm5c-Kdm5d<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-8294","authenticated-orcid":false,"given":"Rebecca M.","family":"Malcore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milan Kumar","family":"Samanta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0763-8050","authenticated-orcid":false,"given":"Sundeep","family":"Kalantry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2280-7422","authenticated-orcid":false,"given":"Shigeki","family":"Iwase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024103001301811000_2024.10.24.620066v1.1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.107052"},{"key":"2024103001301811000_2024.10.24.620066v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2009.03.011"},{"key":"2024103001301811000_2024.10.24.620066v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/gr.275965.121"},{"key":"2024103001301811000_2024.10.24.620066v1.4","doi-asserted-by":"publisher","DOI":"10.1530\/REP-06-0078"},{"key":"2024103001301811000_2024.10.24.620066v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-15931-3"},{"key":"2024103001301811000_2024.10.24.620066v1.6","doi-asserted-by":"publisher","DOI":"10.1242\/dev.117.1.341"},{"key":"2024103001301811000_2024.10.24.620066v1.7","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.1.171"},{"key":"2024103001301811000_2024.10.24.620066v1.8","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0790159"},{"key":"2024103001301811000_2024.10.24.620066v1.9","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00022"},{"key":"2024103001301811000_2024.10.24.620066v1.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0913843107"},{"key":"2024103001301811000_2024.10.24.620066v1.11","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1506-4"},{"key":"2024103001301811000_2024.10.24.620066v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.11.071"},{"key":"2024103001301811000_2024.10.24.620066v1.13","doi-asserted-by":"crossref","unstructured":"Ohno, S . 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