title: Appropriate expression of the mouse H19 gene utilises three or more distinct enhancer regions spread over more than 130 kb.
abstract: H19 and Igf2 are closely linked, reciprocally imprinted genes which lie on distal chromosome 7 in the mouse. Data suggests that common elements are used for expression and imprinting of both genes, and simple models have been proposed based on the presence of a single set of enhancers located downstream of H19. In this study we have investigated the H19 expression pattern from a 130 kb YAC transgene, which imprints H19 appropriately at ectopic loci. However, we show that while enhancers for expression in many cell types are present on the YAC, those for expression in mesodermal components of the heart, kidney, lung and thymus are located at a greater distance. Based on the available evidence, we conclude that regulation of H19 is complex, requiring contribution from at least three different sets of cell-type specific enhancers. Thus, the mechanism of reciprocal imprinting of H19 and Igf2 utilises different regulatory elements in different cell types during mouse development.
authors.affiliation: Wellcome/CRC Institute of Cancer and Developmental Biology, and Physiological laboratory, University of Cambridge, Tennis Court Road, Cambridge, UK. jfxa1@mole.bio.cam.ac.uk
authors.forename: J F
authors.initials: JF
authors.lastname: Ainscough
authors.forename: L
authors.initials: L
authors.lastname: Dandolo
authors.forename: M A
authors.initials: MA
authors.lastname: Surani
mesh_terms: D000818:Animals; D005314:Embryonic and Fetal Development; D004742:Enhancer Elements, Genetic; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins
chemical_list: C094335:H19 long non-coding RNA; C484353:Mrpl23 protein, mouse; D009124:Muscle Proteins; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D007335:Insulin-Like Growth Factor II