title: The mouse Snrpn minimal promoter and its human orthologue: activity and imprinting.
abstract: BACKGROUND
  Microdeletions in chromosome 15q13-15 of Prader-Willi (PWS) and Angelman Syndrome (AS) patients suggested that SNRPN promoter/exon 1, together with a short sequence located approximately 35 kb upstream, constitute an imprinting control centre that regulates the entire 2 Mb PWS/AS imprinted domain. We have recently shown that a minitransgene composed of the human upstream sequence and mouse Snrpn promoter/exon 1 harbours all the elements necessary for establishing and maintaining an imprinted state.
  
  
  RESULTS
  Here we describe, using transfection experiments, the Snrpn minimal promoter (SMP), being composed of the entire 76 bp exon 1 and 84 bp of upstream sequence. A 7 bp element (SBE) within SMP that, in its unmethylated state binds a specific protein, is absolutely required for promoter activity. The orthologous human sequence, in spite of the fact that it possesses an identical SBE, failed to display promoter activity in transfection experiments and failed to create a methylated state of the maternal allele. Transgenic experiments reveal that a mutation in SBE of the mouse sequence did not completely abolish methylation of the maternal allele, indicating that sequences outside SBE participate in this process. Replacement of human exon 1 with the mouse orthologue replenished promoter activity, but left the maternal allele in the transgenic experiment unmethylated. The reciprocal chimera, in which mouse exon 1 was replaced by the human orthologue resulted in loss of promoter activity and did not support differential methylation.
  
  
  CONCLUSIONS
  The observations made by in vitro and in vivo experiments suggest that several cis elements which are involved in Snrpn promoter activity and the imprinting process are present in the mouse promoter and absent in the human orthologous sequence.
authors.affiliation: Department of Cellular Biochemistry and Human Genetics, The Hebrew University Hadassah Medical School, Jerusalem, Israel 91120.
authors.forename: A Y
authors.initials: AY
authors.lastname: Hershko
authors.forename: Y
authors.initials: Y
authors.lastname: Finberg
authors.forename: B
authors.initials: B
authors.lastname: Kantor
authors.forename: R
authors.initials: R
authors.lastname: Shemer
authors.forename: A
authors.initials: A
authors.lastname: Razin
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D018899:CpG Islands; D004247:DNA; D019175:DNA Methylation; D005091:Exons; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D008845:Microinjections; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins; D004247:DNA