Human Molecular Genetics Advance Access originally published online on October 4, 2008
Human Molecular Genetics 2009 18(1):118-127; doi:10.1093/hmg/ddn322
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Transcript- and tissue-specific imprinting of a tumour suppressor gene
1 Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK 2 Clinical and Molecular Genetics, Institute of Child Health, University College London, London WC1N 1EH, UK
* To whom correspondence should be addressed at: Department of Medical and Molecular Genetics, King's College London, Guy's Campus, Guy's Hospital, 8th floor Tower Wing, London SE1 9RT, UK. Tel: +44 207188 3711; Fax: +44 2071882585; 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 organized 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.
Present address: Cancer Research UK Cambridge Research Institute, Cambridge University, Cambridge CB2 0RE, UK.
Present address: Department of Molecular and Cell Biology, University of California at Berkeley, CA 94720-3204, USA.