Analysis of the promoter and transcription start sites of the human thrombospondin 2 gene (THBS2).
To identify features of the human thrombospondin 2 gene (THBS2) important for regulation of expression, the sequences of 5 kb of the promoter/5' flank and 3 kb of transcribed and intronic DNA were determined. Two repetitive sequences were found: an MLT1c element located 2.2 kb 5' of exon 1 and, further 5', 1.8 kb of a Tigger1 element. Putative transcription factor binding sites that might be significant for THBS2 regulation included p53, NF-kappaB, Spl, Myc-CF1, NF-Y, CF1, AP1, and GATA sites. Alignment of the promoter/5' flank sequence with the mouse Thbs2 promoter revealed 78% identity for a 450 bp region immediately upstream from the mouse transcription start site. No significant homology was detected between the human thrombospondin 2 and thrombospondin 1 promoters. Comparison of the THBS2 genomic and cDNA sequences revealed that, in contrast to Thbs2, exon 1 is divided into exons 1A and 1B by a small (93 bp) intron. The transcription start site was investigated by a PCR procedure and by 5' RACE, and yielded a size for exon 1A of at least 186 bp. Tissue-specific differences in transcription start sites were found, with transcript lengths in the order: fetal lung > adult lung > fetal brain. These results suggest that tissue-specific differences in expression of the THBS2 gene may be determined, in part, by selection of the transcription start site and resulting differences in the 5' untranslated region.
Adolph
K W
KW
Department of Biochemistry, University of Minnesota Medical School, Minneapolis 55455, USA.
Liska
D J
DJ
Bornstein
P
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D017124:Conserved Sequence; D005091:Exons; D005786:Gene Expression Regulation; D015698:Genomic Library; D006801:Humans; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D019699:Thrombospondins; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D008562:Membrane Glycoproteins; D019699:Thrombospondins; D014157:Transcription Factors