{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:45:39Z","timestamp":1768517139722,"version":"3.49.0"},"posted":{"date-parts":[[2024,11,18]]},"group-title":"Molecular Biology","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Germline mutations in SMCHD1, DNMT3B and LRIF1 can cause facioscapulohumeral muscular dystrophy type 2 (FSHD2). FSHD is an epigenetic skeletal muscle disorder in which partial failure in heterochromatinization of the D4Z4 macrosatellite repeat causes spurious expression of the repeat-embedded\n                  <jats:italic>DUX4<\/jats:italic>\n                  gene in skeletal muscle, ultimately leading to muscle weakness and wasting. All three proteins play a role in chromatin organization and gene silencing; however, their functional relationship has not been fully elucidated. Here, we show that knockdown of\n                  <jats:italic>Lrif1<\/jats:italic>\n                  , but not of the other two FSHD2 genes, in mouse embryonic stem cells leads to modest upregulation of the 2-cell cleavage stage transcriptional program driven by the transcription factor Dux, which is the mouse functional homologue of human DUX4. Furthermore, we show that Lrif1 interacts with Trim28, a known Dux repressor and that this interaction is independent of Cbx proteins and Smchd1. We uncover that modest\n                  <jats:italic>Dux<\/jats:italic>\n                  upregulation in\n                  <jats:italic>Lrif1<\/jats:italic>\n                  knockdown mESCs coincides with decreased Trim28 occupancy at the\n                  <jats:italic>Dux<\/jats:italic>\n                  locus. Together, our results provide evidence for a conserved function of Lrif1 in repressing an early zygotic genome activator in mice and humans.\n                <\/jats:p>","DOI":"10.1101\/2024.11.18.624083","type":"posted-content","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T21:51:50Z","timestamp":1731966710000},"source":"Crossref","is-referenced-by-count":0,"title":["Lrif1 modulates Trim28-mediated repression of the\n                  <i>Dux<\/i>\n                  locus in mouse embryonic stem cells"],"prefix":"10.64898","author":[{"given":"Darina","family":"\u0160ikrov\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rom\u00e1n","family":"Gonz\u00e1lez-Prieto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred C. O.","family":"Vertegaal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judit","family":"Balog","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Clemens-Daxinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-711X","authenticated-orcid":false,"given":"Silv\u00e8re M.","family":"van der Maarel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024112022252306000_2024.11.18.624083v1.1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-221624"},{"key":"2024112022252306000_2024.11.18.624083v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/dnares\/dsv013"},{"key":"2024112022252306000_2024.11.18.624083v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.087."},{"key":"2024112022252306000_2024.11.18.624083v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.10.019"},{"key":"2024112022252306000_2024.11.18.624083v1.5","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz594"},{"key":"2024112022252306000_2024.11.18.624083v1.6","doi-asserted-by":"crossref","unstructured":"Genet M , Torres-Padilla ME : The molecular and cellular features of 2-cell-like cells: a reference guide. Development 2020, 147(16).","DOI":"10.1242\/dev.189688"},{"key":"2024112022252306000_2024.11.18.624083v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3066"},{"key":"2024112022252306000_2024.11.18.624083v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3844"},{"key":"2024112022252306000_2024.11.18.624083v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.043"},{"key":"2024112022252306000_2024.11.18.624083v1.10","doi-asserted-by":"crossref","unstructured":"Huang Z , Yu J , Cui W , Johnson BK , Kim K , Pfeifer GP : The chromosomal protein SMCHD1 regulates DNA methylation and the 2c-like state of embryonic stem cells by antagonizing TET proteins. Sci Adv 2021, 7(4).","DOI":"10.1126\/sciadv.abb9149"},{"key":"2024112022252306000_2024.11.18.624083v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.10.001"},{"key":"2024112022252306000_2024.11.18.624083v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3858"},{"key":"2024112022252306000_2024.11.18.624083v1.13","doi-asserted-by":"publisher","DOI":"10.1101\/gad.321174.118"},{"key":"2024112022252306000_2024.11.18.624083v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21340"},{"key":"2024112022252306000_2024.11.18.624083v1.15","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjy040"},{"key":"2024112022252306000_2024.11.18.624083v1.16","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00432-15"},{"key":"2024112022252306000_2024.11.18.624083v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2532"},{"key":"2024112022252306000_2024.11.18.624083v1.18","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2019.0334"},{"key":"2024112022252306000_2024.11.18.624083v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901318116"},{"key":"2024112022252306000_2024.11.18.624083v1.20","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2006-7-7-228"},{"key":"2024112022252306000_2024.11.18.624083v1.21","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-6-15"},{"key":"2024112022252306000_2024.11.18.624083v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature08674"},{"key":"2024112022252306000_2024.11.18.624083v1.23","doi-asserted-by":"publisher","DOI":"10.1101\/gr.147678.112"},{"key":"2024112022252306000_2024.11.18.624083v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-021-00590-w"},{"key":"2024112022252306000_2024.11.18.624083v1.25","first-page":"385","article-title":"Retinoic Acid Induces Embryonic Stem Cells (ESCs) Transition to 2 Cell-Like State Through a Coordinated Expression of Dux and Duxbl1","volume":"7","year":"2019","journal-title":"Front Cell Dev Biol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.11.18.624083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T07:28:58Z","timestamp":1768462138000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.11.18.624083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":25,"URL":"https:\/\/doi.org\/10.1101\/2024.11.18.624083","relation":{},"subject":[],"published":{"date-parts":[[2024,11,18]]},"subtype":"preprint"}}