Regulation of alternative polyadenylation by genomic imprinting.
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.
Wood
Andrew J
AJ
Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London SE1 9RT, United Kingdom.
Schulz
Reiner
R
Woodfine
Kathryn
K
Koltowska
Katarzyna
K
Beechey
Colin V
CV
Peters
Jo
J
Bourc'his
Deborah
D
Oakey
Rebecca J
RJ
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
C108856:H13 protein, mouse; D015778:Minor Histocompatibility Antigens; D011061:Poly A