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Human Molecular Genetics Advance Access published online on October 4, 2008
Human Molecular Genetics, doi:10.1093/hmg/ddn322
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© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Transcript- and tissue-specific imprinting of a tumour suppressor gene

Reiner Schulz1, Ruth McCole1, Kathryn Woodfine1,3, Andrew J. Wood1,4, Mandeep Chahal1, David Monk2, Gudrun E. Moore2 and Rebecca J. Oakey1,*

1 Department of Medical & Molecular Genetics, King's College London, London SE1 9RT, UK 2 Clinical and Molecular Genetics, Institute of Child Health, University College London, London WC1 N 1EH, UK 3 Presently at: Cancer Research UK Cambridge Research Institute, Cambridge University, Cambridge CB2 0RE, UK 4 Presently at: Department of Molecular and Cell Biology, University of California at Berkeley, CA 94720-3204, USA

* Corresponding author: Department of Medical & Molecular Genetics, King's College London, Guy's Campus, Guy's Hospital, 8th floor Tower Wing, London SE1 9RT, UK; phone: +44 020 7188 3711, fax: +44 020 7188 2585, email: rebecca.oakey{at}genetics.kcl.ac.uk

Received June 25, 2008; Revised September 21, 2008; Accepted October 2, 2008

The Bladder Cancer-Associated Protein gene (BLCAP; previously BC10) is a tumour suppressor that limits cell proliferation and stimulates apoptosis. BLCAP protein or message are downregulated or absent in a variety of human cancers. In mouse and human, the first intron of Blcap/BLCAP contains the distinct Neuronatin (Nnat/NNAT) gene. Nnat is an imprinted gene that is exclusively expressed from the paternally inherited allele. Previous studies found no evidence for imprinting of Blcap in mouse or human. Here we show that Blcap is imprinted in mouse and human brain, but not in other mouse tissues. Moreover, Blcap produces multiple distinct transcripts that exhibit reciprocal allele-specific expression in both mouse and human. We propose that the tissue-specific imprinting of Blcap is due to the particularly high transcriptional activity of Nnat in brain, as has been suggested previously for the similarly organised and imprinted murine Commd1/U2af1-rs1 locus. For Commd1/U2af1-rs1 we show that it too produces distinct transcript variants with reciprocal allele-specific expression. The imprinted expression of BLCAP and its interplay with NNAT at the transcriptional level may be relevant to human carcinogenesis.


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