{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:11:56Z","timestamp":1792599116803,"version":"4.5.0"},"reference-count":97,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-156048"],"award-info":[{"award-number":["PJT-156048"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Dimorphism of sex chromosomes often leads to a need for dosage compensation. In eutherian mammals, XIST, a long non-coding RNA, is expressed from the X chromosome that will be silenced, triggering X-chromosome inactivation (XCI). XIST originated from the ancestral protein-coding Lnx3 gene with contributions from various mobile elements that contributed to the striking domains of tandem repeats within the first and sixth exons. Modular domains of XIST are now involved in recruiting heterochromatic marks and proteins essential for XCI initiation and maintenance. This review presents a comparative analysis of human XIST with five other eutherian mammals\u2014chimpanzees, cats, pigs, sheep, and mice\u2014examining conservation across exons as well as the tandem repeats. Notably, repeats exhibited higher conservation than exons, underscoring their functional importance. Additionally, a species-specific G repeat, previously described in pigs, was also identified in sheep and cats. These findings provide insights into the domains of XIST, a cis-acting silencer that has been used to proposed to alleviate the impact of a supernumerary chromosome in Down syndrome.<\/jats:p>","DOI":"10.3390\/ncrna11030035","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T09:16:12Z","timestamp":1746090972000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Human XIST: Origin and Divergence of a cis-Acting Silencing RNA"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1609-522X","authenticated-orcid":false,"given":"Maria Jose","family":"Navarro-Cobos","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8959-0101","authenticated-orcid":false,"given":"Carolyn J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Molecular Epigenetics Group, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41576-024-00757-3","article-title":"Evolution and regulation of animal sex chromosomes","volume":"26","author":"Zhu","year":"2025","journal-title":"Nat. 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