Regulation of alternative polyadenylation by genomic imprinting
- Andrew J. Wood1,4,
- Reiner Schulz1,
- Kathryn Woodfine1,
- Katarzyna Koltowska1,
- Colin V. Beechey2,
- Jo Peters2,
- Deborah Bourc’his3, and
- Rebecca J. Oakey1,5
- 1 Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London SE1 9RT, United Kingdom;
- 2 Medical Research Council Mammalian Genetics Unit, Harwell OX11 0RD, United Kingdom;
- 3 Institut National de la Santé et de la Recherche Médicale (INSERM) U741, Institut Jacques Monod, 75251 Paris, Cedex 05, France
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.
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Footnotes
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↵4 Present address: Department of Molecular Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
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↵5 Corresponding author.
↵5 E-MAIL rebecca.oakey{at}kcl.ac.uk; FAX 44-207188-2585.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.473408.
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- Received January 28, 2008.
- Accepted March 10, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press
