{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:23:06Z","timestamp":1791202986638,"version":"4.2.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"16","license":[{"start":{"date-parts":[[2000,8,15]],"date-time":"2000-08-15T00:00:00Z","timestamp":966297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The H19 imprinted gene is silenced when paternally inherited and active only when inherited maternally. This is thought to involve a cis-acting control region upstream of H19 that is responsible for regulating a number of functions including DNA methylation, asynchronous replication of parental chromosomes and an insulator. Here we report on the function of a 1.2 kb upstream element in the mouse, which was previously shown to function as a bi-directional silencer in Drosophila. The cre-loxP-mediated targeted deletion of the 1.2 kb region had no effect on the maternal allele. However, there was loss of silencing of the paternal allele in many endodermal and other tissues. The pattern of expression was very similar to the expression pattern conferred by the enhancer elements downstream of H19. We could not detect an effect on the expression of the neighbouring imprinted Igf2 gene, suggesting that the proposed boundary element insulating this gene from the downstream enhancers was unaffected. Despite derepression of the paternal H19 allele, the deletion surprisingly did not affect the differential DNA methylation of the locus, which displayed an appropriate epigenetic switch in the parental germlines. Furthermore, the characteristic asynchronous pattern of DNA replication at H19 was also not disrupted by the deletion, suggesting that the sequences that mediate this were also intact. The silencer is therefore part of a complex cis-regulatory region upstream of the H19 gene and acts specifically to ensure the repression of the paternal allele, without a predominant effect on the epigenetic switch in the germline.<\/jats:p>","DOI":"10.1242\/dev.127.16.3419","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T04:13:40Z","timestamp":1619410420000},"page":"3419-3428","source":"Crossref","is-referenced-by-count":77,"title":["Deletion of a silencer element disrupts<i>H19<\/i>imprinting independently of a DNA methylation epigenetic switch"],"prefix":"10.1242","volume":"127","author":[{"given":"Robert A.","family":"Drewell","sequence":"first","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Brenton","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin F.-X.","family":"Ainscough","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila C.","family":"Barton","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy J.","family":"Hilton","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharine L.","family":"Arney","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Dandolo","sequence":"additional","affiliation":[{"name":"2 Institut Cochin de G\u00e9n\u00e9tique Mol\u00e9culaire (ICGM), Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U257, Paris 75014, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Azim","family":"Surani","sequence":"additional","affiliation":[{"name":"University of Cambridge 1 Wellcome\/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory , , Tennis Court Road, Cambridge, CB2 1QR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2000,8,15]]},"reference":[{"key":"2023030202553927500_","doi-asserted-by":"publisher","first-page":"3621","DOI":"10.1242\/dev.124.18.3621","article-title":"Imprinting of Igf2 and H19 from a 130 kb YAC transgene","volume":"124","author":"Ainscough","year":"1997","journal-title":"Development"},{"key":"2023030202553927500_","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/S0925-4773(99)00289-0","article-title":"Appropriate expression of the mouse H19 gene utilises three or more distinct enhancer regions spread over more than 130 kb","volume":"91","author":"Ainscough","year":"2000","journal-title":"Mech. 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