Abstract
The BTB/POZ transcriptional repressor HIC1 (Hypermethylated in Cancer 1) is a tumor suppressor gene located at chromosome 17p13.3, a region frequently hypermethylated or deleted in human tumors and in a contiguous-gene syndrome, the Miller–Dieker syndrome. The human and murine HIC1 genes are composed of two alternative 5′ exons, 1a and 1b fused to a large second coding exon 2. Exon 1a is a noncoding exon associated with a major G–C-rich promoter whereas exon 1b is a downstream coding exon associated with a minor TATA box promoter. By human–mouse genome comparison, we have identified a short upstream conserved sequence containing G–C boxes which were shown to be functional. Transcripts initiating from this new promoter were detected in various human and mouse tissues and contained a long 5′-UTR sequence, called 1c which encompass the G–C-rich promoter associated with exon 1a and uses the same splice donor site. RT–PCR analyses of two primary breast epithelial cell lines identified two other 5′-UTRs generated by alternative splicing within exon 1c. Our results thus highlight the existence of an unexpected complex transcriptional regulation of HIC1.
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Acknowledgements
This work was supported by funds from CNRS, the PASTEUR Institute, Ligue Régionale contre le Cancer (Comité de l'Aisne) and a grant from the NIH (Ovarian Cancer SPORE P50 CA83638). We thank Patrick Dumont for dissection of mouse tissues and Agnès Bègue for the murine ovaries cDNA fractions. We also thank Agnès Bègue, Jean Coll and Brian Rood for their comments on the manuscript.
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The nucleotide sequences reported in this paper have been deposited to the EMBL database under Accession Numbers: AJ414163, AJ550616, AJ585343, AJ583693, AJ583594 and AJ585343
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Pinte, S., Guérardel, C., Deltour-Balerdi, S. et al. Identification of a second G–C-rich promoter conserved in the human, murine and rat tumor suppressor genes HIC1. Oncogene 23, 4023–4031 (2004). https://doi.org/10.1038/sj.onc.1207504
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DOI: https://doi.org/10.1038/sj.onc.1207504
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