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.
Pinte
Sébastien
S
CNRS UMR 8526, Institut de Biologie de Lille, Institut Pasteur de Lille, 1 Rue Calmette, 59017 Lille, France.
Guérardel
Cateline
C
Deltour-Balerdi
Sophie
S
Godwin
Andrew K
AK
Leprince
Dominique
D
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