Sequences promoting the transcription of the human XA gene overlapping P450c21A correctly predict the presence of a novel, adrenal-specific, truncated form of tenascin-X.
A compact region in the human class III major histocompatibility locus contains the human genes for the fourth component of human complement (C4) and steroid 21-hydroxylase (P450c21) in one transcriptional orientation, while the gene for the extracellular matrix protein tenascin-X (TN-X) overlaps the last exon of P450c21 on the opposite strand of DNA in the opposite transcriptional orientation. This complex locus is duplicated into A and B loci, so that the organization is 5'-C4A-21A-XA-C4B-21B-XB-3'. Although this duplication event truncated the 65-kb X(B) gene to a 4.5-kb XA gene, the XA gene is transcriptionally active in the adrenal cortex. To examine the basis of the tissue-specific expression of XA and C4B, we cloned the 1763-bp region that lies between the cap sites for XA and C4B and analyzed its promoter activity in both the XA and the C4 orientations. Powerful, liver-specific sequences lie within the first 75 to 138 bp from the C4B cap site, and weaker elements lie within 128 bp of the XA cap site that function in both liver and adrenal cells. Because these 128 bp upstream from the XA cap site are perfectly preserved in the XB gene encoding TN-X, we sought to determine whether a transcript similar to XA arises within the XB gene. RNase protection assays, cDNA cloning, and RT/PCR show that adrenal cells contain a novel transcript, termed short XB (XB-S), which has the same open reading frame as TN-X.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of California, San Francisco 94143-0978, USA.
M K
MK
Tee
A A
AA
Thomson
J
J
Bristow
W L
WL
Miller
D000302:Adrenal Cortex / Q000737:chemistry*; D000595:Amino Acid Sequence; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D005340:Fibrinogen / Q000737:chemistry; D005796:Genes; D005807:Genes, Overlapping; D006801:Humans; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D019063:Tenascin / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D010446:Peptide Fragments; D011506:Proteins; C074149:TNXA protein, human; D019063:Tenascin; C081865:tenascin X; D005340:Fibrinogen; D013255:Steroid 21-Hydroxylase