{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:33:34Z","timestamp":1773146014149,"version":"3.50.1"},"reference-count":42,"publisher":"The Company of Biologists","issue":"10","license":[{"start":{"date-parts":[[1994,10,1]],"date-time":"1994-10-01T00:00:00Z","timestamp":780969600000},"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":[[1994,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The Insulin-like growth factor 2 (Igf2) and H19 genes are reciprocally imprinted and closely linked. Igf2 encodes a fetal growth-factor and is predominantly expressed from the paternal allele, while H19 is expressed from the maternal allele and encodes a transcript which may down-regulate cellular proliferation. One of the epigenetic modifications thought to be involved in parental imprinting is DNA methylation. Here we analyse methylation in two regions of the Igf2 gene, one approx. 3 kb upstream of the gene and one in the 3\u2032 part of the gene. Both regions are more methylated on the expressed paternal chromosome. Genomic sequencing of individual chromosomes in the first region shows this parent-specific methylation to be highly mosaic; interestingly, individual sperm chromosomes carry different methylation patterns into the egg. In the more 3\u2032 region, which is fully methylated in sperm, the level of methylation on the paternal allele is highly tissue-specific and is correlated with expression of the gene in fetal tissues. Hence, the paternal allele is highly methylated in fetal liver (high expression) but is undermethylated in fetal brain (virtually no expression). Adult choroid plexus, a brain tissue in which Igf2 is expressed from both alleles and H19 is not expressed, represents an apparent loss of imprinting. Here, both Igf2 and H19 adopt a paternal type methylation pattern on both parental chromosomes. Analysis of early-passage androgenetic and parthenogenetic embryonic stem (ES) cells shows that the methylation patterns of Igf2 and H19 on maternal and paternal chromosomes are very similar. Androgenetic and parthenogenetic teratomas derived from these ES cells show the appropriate paternal and maternal patterns, respectively, of allelic methylation in both genes. Our results suggest that allelic methylation patterns in Igf2 and H19 arise early in embryogenesis and change progressively during development. Some of these developmental changes are apparently under tissue-specific control.<\/jats:p>","DOI":"10.1242\/dev.120.10.2933","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T01:32:39Z","timestamp":1619400759000},"page":"2933-2943","source":"Crossref","is-referenced-by-count":225,"title":["Developmental control of allelic methylation in the imprinted mouse <i>Igf2<\/i> and <i>H19<\/i> genes"],"prefix":"10.1242","volume":"120","author":[{"given":"Robert","family":"Feil","sequence":"first","affiliation":[{"name":"Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK"}]},{"given":"J\u00f6rn","family":"Walter","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK"}]},{"given":"Nicholas D.","family":"Allen","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK"}]},{"given":"Wolf","family":"Reik","sequence":"additional","affiliation":[{"name":"Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge CB2 4AT, UK"}]}],"member":"237","published-online":{"date-parts":[[1994,10,1]]},"reference":[{"key":"2024121723475625700_DEVELOP_120_10_2933C1","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1242\/dev.120.6.1473","article-title":"A functional analysis of imprinting in parthenogenetic embryonic stem cells","volume":"120","author":"Allen","year":"1994","journal-title":"Development"},{"key":"2024121723475625700_DEVELOP_120_10_2933C2","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/349084a0","article-title":"The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus","volume":"349","author":"Barlow","year":"1991","journal-title":"Nature"},{"key":"2024121723475625700_DEVELOP_120_10_2933C3","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/351153a0","article-title":"Parental imprinting of the mouse H19 gene","volume":"351","author":"Bartolomei","year":"1991","journal-title":"Nature"},{"key":"2024121723475625700_DEVELOP_120_10_2933C4","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1101\/gad.7.9.1663","article-title":"Epigenetic mechanisms underlying the imprinting of the mouse H19 gene","volume":"7","author":"Bartolomei","year":"1993","journal-title":"Genes Dev"},{"key":"2024121723475625700_DEVELOP_120_10_2933C5","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.1002\/j.1460-2075.1993.tb06041.x","article-title":"The ontogeny of allele-specific methylation associated with imprinted genes in the mouse","volume":"12","author":"Brandeis","year":"1993","journal-title":"EMBO J"},{"key":"2024121723475625700_DEVELOP_120_10_2933C6","first-page":"63","article-title":"Autosomal and X-chromosome imprinting","volume-title":"Development","author":"Cattanach","year":"1990"},{"key":"2024121723475625700_DEVELOP_120_10_2933C7","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/ng1292-270","article-title":"A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression","volume":"2","author":"Cattanach","year":"1992","journal-title":"Nature Genet"},{"key":"2024121723475625700_DEVELOP_120_10_2933C8","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/0003-2697(87)90021-2","article-title":"Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Analyt. 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Acids Res"},{"key":"2024121723475625700_DEVELOP_120_10_2933C12","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/ng0693-110","article-title":"Genomic imprinting and gene activation in cancer","volume":"4","author":"Feinberg","year":"1993","journal-title":"Nature Genet"},{"key":"2024121723475625700_DEVELOP_120_10_2933C13","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/362751a0","article-title":"Parental-origin-specific epigenetic modification of the H19 gene","volume":"362","author":"Ferguson-Smith","year":"1993","journal-title":"Nature"},{"key":"2024121723475625700_DEVELOP_120_10_2933C14","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1073\/pnas.89.5.1827","article-title":"A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands","volume":"89","author":"Frommer","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024121723475625700_DEVELOP_120_10_2933C15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng0394-310","article-title":"Allele-specific inactivation of Insulin 1 and 2, in the mouse yolk sac indicates imprinting","volume":"6","author":"Giddings","year":"1994","journal-title":"Nature Genet"},{"key":"2024121723475625700_DEVELOP_120_10_2933C16","doi-asserted-by":"publisher","first-page":"5577","DOI":"10.1093\/nar\/21.24.5577","article-title":"A new imprinted gene cloned by a methylation-sensitive genomic scanning method","volume":"21","author":"Hatada","year":"1993","journal-title":"Nucl. 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Genet"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/120\/10\/2933\/3594231\/develop_120_10_2933.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/120\/10\/2933\/3594231\/develop_120_10_2933.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T23:48:17Z","timestamp":1734479297000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/120\/10\/2933\/38153\/Developmental-control-of-allelic-methylation-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,10,1]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[1994,10,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.120.10.2933","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,10,1]]}}}