title: Regulation of alternative polyadenylation by genomic imprinting.
abstract: Maternally and paternally derived alleles can utilize different promoters, but allele-specific differences in cotranscriptional processes have not been reported. We show that alternative polyadenylation sites at a novel murine imprinted gene (H13) are utilized in an allele-specific manner. A differentially methylated CpG island separates polyA sites utilized on maternal and paternal alleles, and contains an internal promoter. Two genetic systems show that alleles lacking methylation generate truncated H13 transcripts that undergo internal polyadenylation. On methylated alleles, the internal promoter is inactive and elongation proceeds to downstream polyadenylation sites. This demonstrates that epigenetic modifications can influence utilization of alternative polyadenylation sites.
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wood
authors.forename: Reiner
authors.initials: R
authors.lastname: Schulz
authors.forename: Kathryn
authors.initials: K
authors.lastname: Woodfine
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Koltowska
authors.forename: Colin V
authors.initials: CV
authors.lastname: Beechey
authors.forename: Jo
authors.initials: J
authors.lastname: Peters
authors.forename: Deborah
authors.initials: D
authors.lastname: Bourc'his
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Oakey
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D008957:Models, Genetic; D011061:Poly A / Q000235:genetics*; D026723:Polyadenylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C108856:H13 protein, mouse; D015778:Minor Histocompatibility Antigens; D011061:Poly A