title: H19ICR mediated transcriptional silencing does not require target promoter methylation.
abstract: Transcription of the reciprocally imprinted genes Insulin-like growth factor 2 (Igf2) and H19 is orchestrated by the 2.4-kb H19 Imprinting Control Region (H19ICR) located upstream of H19. Three known functions are associated with the H19ICR: (1) it is a germline differentially methylated region, (2) it is a transcriptional insulator, and (3) it is a transcriptional silencer. The molecular mechanisms of the DMR and insulator functions have been well characterized but the basis for the ICR's silencer function is less well understood. In order to study the role the H19ICR intrinsically plays in gene silencing, we transferred the 2.4-kb H19ICR to a heterologous non-imprinted location on chromosome 5, upstream of the alpha fetoprotein (Afp) promoter. Independent of its orientation, the 2.4-kb H19ICR silences transcription from the paternal Afp promoter. Thus silencing is a function intrinsic to this DNA element. Further, ICR mediated silencing is a developmental process that, unexpectedly, does not occur through DNA methylation at the target promoter.
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gebert
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Rong
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sangkyun
authors.initials: S
authors.lastname: Jeong
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: James
authors.initials: J
authors.lastname: Iben
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pfeiferk@mail.nih.gov.
authors.forename: Karl
authors.initials: K
authors.lastname: Pfeifer
mesh_terms: D000818:Animals; D019175:DNA Methylation; D020868:Gene Silencing; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics; D014158:Transcription, Genetic; D000509:alpha-Fetoproteins / Q000235:genetics
chemical_list: C094335:H19 long non-coding RNA; C513121:IGF2 protein, mouse; D062085:RNA, Long Noncoding; D000509:alpha-Fetoproteins; D007335:Insulin-Like Growth Factor II
keywords: DNA methylation; Gene silencing; Genomic imprinting; H19