Identification of a second G-C-rich promoter conserved in the human, murine and rat tumor suppressor genes HIC1.
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.
CNRS UMR 8526, Institut de Biologie de Lille, Institut Pasteur de Lille, 1 Rue Calmette, 59017 Lille, France.
Sébastien
S
Pinte
Cateline
C
Guérardel
Sophie
S
Deltour-Balerdi
Andrew K
AK
Godwin
Dominique
D
Leprince
D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D010053:Ovary / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D014157:Transcription Factors / Q000235:genetics*
C096870:Hic1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors