Transcript- and tissue-specific imprinting of a tumour suppressor gene.
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.
Schulz
Reiner
R
Department of Medical and Molecular Genetics, King's College London, London SE1 9RT, UK.
McCole
Ruth B
RB
Woodfine
Kathryn
K
Wood
Andrew J
AJ
Chahal
Mandeep
M
Monk
David
D
Moore
Gudrun E
GE
Oakey
Rebecca J
RJ
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D019175:DNA Methylation; D005333:Fetus / Q000378:metabolism; D018392:Genomic Imprinting; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C453739:BLCAP protein, human; C529498:Blcap protein, mouse; D008565:Membrane Proteins; C490237:NNAT protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C490239:Nnat protein, mouse; D025521:Tumor Suppressor Proteins