Structure and expression of the human apolipoprotein A-IV gene

N. A. Elshourbagy, D. W. Walker, Young-Ki Paik, M. S. Boguski, M. Freeman, J. I. Gordon, J. M. Taylor

Research output: Contribution to journalArticle

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Abstract

We have isolated the human apolipoprotein (apo) A-IV gene from a cosmid library and determined its complete nucleotide sequence. The gene contains three exons of 162, 127, and 1180 nucleotides separated by two introns of 357 and 777 nucleotides. A sequence polymorphism has been identified in the 3' noncoding portion of the third exon. The human apoA-IV gene lacks an intron in the area encoding the 5' nontranslated region of its mRNA, which distinguishes it from all the other human apolipoprotein genes whose sequences are known. Comparison matrix analysis of the human apoA-IV gene sequence revealed evidence for an ancestral 11-nucleotide repeat unit that spans the third exon. These repeated sequences are much more highly conserved than those present in either rat apoA-IV or in any other human apolipoprotein. Optimal alignments of the 5' flanking regions of the rat and human apoA-IV genes disclosed multiple deletions in the rat sequence as well as a highly conserved region of 90 nucleotides (90% sequence identity) located within 170 nucleotides of the start site of transcription. The 5' flanking regions of the human and rat apoA-IV genes were ligated to the bacterial chloramphenicol acetyltransferase gene, then transfected into different cultured cells. The apoA-IV gene sequences elicited preferential expression of chloramphenicol acetyltransferase activity when introduced into intestinally derived Caco-2 cells and liver-derived Hep-G2 cells, consistent with the tissue specificity of the native gene. Analysis of deletion mutants of the human apoA-IV 5' flanking region indicated that regions from -293 to -233 and from -127 to -60 upstream of the transcription start site contain sequences required for maximum gene expression. These findings on the structure and expression of rat and human apoA-IV should prove useful in studying the control of the apoA-IV gene.

Original languageEnglish
Pages (from-to)7973-7981
Number of pages9
JournalJournal of Biological Chemistry
Volume262
Issue number17
Publication statusPublished - 1987 Sep 15

Fingerprint

Apolipoproteins A
Genes
Nucleotides
Rats
5' Flanking Region
Exons
Chloramphenicol O-Acetyltransferase
Apolipoproteins
Transcription Initiation Site
Introns
apolipoprotein A-IV
Cosmids
Organ Specificity
Caco-2 Cells
Hep G2 Cells
Polymorphism
Gene expression
Liver
Cultured Cells
Cells

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Elshourbagy, N. A., Walker, D. W., Paik, Y-K., Boguski, M. S., Freeman, M., Gordon, J. I., & Taylor, J. M. (1987). Structure and expression of the human apolipoprotein A-IV gene. Journal of Biological Chemistry, 262(17), 7973-7981.
Elshourbagy, N. A. ; Walker, D. W. ; Paik, Young-Ki ; Boguski, M. S. ; Freeman, M. ; Gordon, J. I. ; Taylor, J. M. / Structure and expression of the human apolipoprotein A-IV gene. In: Journal of Biological Chemistry. 1987 ; Vol. 262, No. 17. pp. 7973-7981.
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Elshourbagy, NA, Walker, DW, Paik, Y-K, Boguski, MS, Freeman, M, Gordon, JI & Taylor, JM 1987, 'Structure and expression of the human apolipoprotein A-IV gene', Journal of Biological Chemistry, vol. 262, no. 17, pp. 7973-7981.

Structure and expression of the human apolipoprotein A-IV gene. / Elshourbagy, N. A.; Walker, D. W.; Paik, Young-Ki; Boguski, M. S.; Freeman, M.; Gordon, J. I.; Taylor, J. M.

In: Journal of Biological Chemistry, Vol. 262, No. 17, 15.09.1987, p. 7973-7981.

Research output: Contribution to journalArticle

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AU - Elshourbagy, N. A.

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N2 - We have isolated the human apolipoprotein (apo) A-IV gene from a cosmid library and determined its complete nucleotide sequence. The gene contains three exons of 162, 127, and 1180 nucleotides separated by two introns of 357 and 777 nucleotides. A sequence polymorphism has been identified in the 3' noncoding portion of the third exon. The human apoA-IV gene lacks an intron in the area encoding the 5' nontranslated region of its mRNA, which distinguishes it from all the other human apolipoprotein genes whose sequences are known. Comparison matrix analysis of the human apoA-IV gene sequence revealed evidence for an ancestral 11-nucleotide repeat unit that spans the third exon. These repeated sequences are much more highly conserved than those present in either rat apoA-IV or in any other human apolipoprotein. Optimal alignments of the 5' flanking regions of the rat and human apoA-IV genes disclosed multiple deletions in the rat sequence as well as a highly conserved region of 90 nucleotides (90% sequence identity) located within 170 nucleotides of the start site of transcription. The 5' flanking regions of the human and rat apoA-IV genes were ligated to the bacterial chloramphenicol acetyltransferase gene, then transfected into different cultured cells. The apoA-IV gene sequences elicited preferential expression of chloramphenicol acetyltransferase activity when introduced into intestinally derived Caco-2 cells and liver-derived Hep-G2 cells, consistent with the tissue specificity of the native gene. Analysis of deletion mutants of the human apoA-IV 5' flanking region indicated that regions from -293 to -233 and from -127 to -60 upstream of the transcription start site contain sequences required for maximum gene expression. These findings on the structure and expression of rat and human apoA-IV should prove useful in studying the control of the apoA-IV gene.

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Elshourbagy NA, Walker DW, Paik Y-K, Boguski MS, Freeman M, Gordon JI et al. Structure and expression of the human apolipoprotein A-IV gene. Journal of Biological Chemistry. 1987 Sep 15;262(17):7973-7981.