{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:10:52Z","timestamp":1768695052752,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,24]]},"group-title":"Developmental Biology","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T00:00:00Z","timestamp":1732406400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>C. elegans<\/jats:italic>\n                  nuclear hormone receptor\n                  <jats:italic>sex-1<\/jats:italic>\n                  is known to be an embryonic X-signal element that represses\n                  <jats:italic>xol-1<\/jats:italic>\n                  , the sex-switch gene that is the master regulator of sex determination and dosage compensation. Several prior studies on\n                  <jats:italic>sex-1<\/jats:italic>\n                  function have suggested that\n                  <jats:italic>sex-1<\/jats:italic>\n                  may have additional downstream roles beyond the regulation of\n                  <jats:italic>xol-1<\/jats:italic>\n                  expression. In this study we characterize some of these additional roles of\n                  <jats:italic>sex-1<\/jats:italic>\n                  in regulating the dual processes of sex determination and dosage compensation during embryogenesis. Our study reveals that\n                  <jats:italic>sex-1<\/jats:italic>\n                  acts on many of the downstream targets of\n                  <jats:italic>xol-1<\/jats:italic>\n                  in a\n                  <jats:italic>xol-1<\/jats:italic>\n                  -independent manner. Further analysis of these shared but independently regulated downstream targets uncovered that\n                  <jats:italic>sex-1<\/jats:italic>\n                  mediates the expression of hermaphrodite- and male-biased genes during embryogenesis. We validated\n                  <jats:italic>sex-1<\/jats:italic>\n                  binding on one of these downstream targets, the male-developmental gene\n                  <jats:italic>her-1.<\/jats:italic>\n                  Our data suggests a model where\n                  <jats:italic>sex-1<\/jats:italic>\n                  exhibits multi-level direct transcriptional regulation on several targets, including\n                  <jats:italic>xol-1<\/jats:italic>\n                  and genes downstream of\n                  <jats:italic>xol-1,<\/jats:italic>\n                  to reinforce the appropriate expression of sex-biased transcripts in XX embryos. Furthermore, we found that\n                  <jats:italic>xol-1 sex-1<\/jats:italic>\n                  double mutants show defects in dosage compensation. Our study provides evidence that misregulation of\n                  <jats:italic>dpy-21<\/jats:italic>\n                  , one of the components of the dosage compensation complex, and the subsequent misregulation of H4K20me1 enrichment on the X chromosomes, may contribute to this defect.\n                <\/jats:p>","DOI":"10.1101\/2024.11.23.624987","type":"posted-content","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:05:13Z","timestamp":1732493113000},"source":"Crossref","is-referenced-by-count":1,"title":["Multi-level transcriptional regulation of embryonic sex determination and dosage compensation by the X-signal element\n                  <i>sex-1<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-5126","authenticated-orcid":false,"given":"Eshna","family":"Jash","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6950-7665","authenticated-orcid":false,"given":"Zoey M.","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9268-1723","authenticated-orcid":false,"given":"Audry I.","family":"Rakozy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4670-5000","authenticated-orcid":false,"given":"Anati 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