title: A silencer element identified in Drosophila is required for imprinting of H19 reporter transgenes in mice.
abstract: The H19 gene is subject to genomic imprinting because it is methylated and repressed after paternal inheritance and is unmethylated and expressed after maternal inheritance. We recently identified a 1.1-kb control element in the upstream region of the H19 gene that functions as a cis-acting silencer element in Drosophila. Here we investigate the function of this element in mice. We demonstrate that both H19-lacZ and H19-PLAP reporter transgenes can undergo imprinting with repression and hypermethylation after paternal transmission at many integration sites. However, transgenes that were deleted for the 1.1-kb silencer element showed loss of paternal repression, but they did not show marked changes in the paternal methylation of the remaining upstream region. This study demonstrates that the 1.1-kb control element identified in Drosophila is required to silence paternally transmitted H19 minitransgenes in mice.
authors.affiliation: Wellcome/Cancer Research Campaign Institute of Cancer and Developmental Biology and Physiological Laboratory, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, United Kingdom.
authors.forename: J D
authors.initials: JD
authors.lastname: Brenton
authors.forename: R A
authors.initials: RA
authors.lastname: Drewell
authors.forename: S
authors.initials: S
authors.lastname: Viville
authors.forename: K J
authors.initials: KJ
authors.lastname: Hilton
authors.forename: S C
authors.initials: SC
authors.lastname: Barton
authors.forename: J F
authors.initials: JF
authors.lastname: Ainscough
authors.forename: M A
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D000818:Animals; D002874:Chromosome Mapping; D019175:DNA Methylation; D004330:Drosophila / Q000235:genetics*; D005260:Female; D015723:Gene Library; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D005821:Genetic Techniques; D018392:Genomic Imprinting; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D013737:Testis / Q000201:enzymology; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C094335:H19 long non-coding RNA; D007527:Isoenzymes; D009124:Muscle Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C055791:germ-cell AP isoenzyme; D000469:Alkaline Phosphatase; D001616:beta-Galactosidase