Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter

L. J. Hall, Y. Kajimoto, D. Bichell, S. W. Kim, P. L. James, D. Counts, L. J. Nixon, G. Tobin, P. Rotwein

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Insulin-like growth factor I (IGF-I) mediates many of the systemic growth- promoting effects of growth hormone and also functions as a locally acting growth stimulator. In mammals, IGF-I gene expression is complicated, as the gene is transcribed and processed into multiple mRNAs (ranging in length from less than 1 to nearly 7.5 kb) that encode at least two protein precursors. As a step toward understanding the regulation of IGF-I, we report the complete organization of the rat IGF-I gene, including identification of the structural determinants for all IGF-I mRNA species, and an initial functional analysis of its promoters. The gene is composed of 6 exons distributed over nearly 80 kb of chromosomal DNA and is structurally heterogeneous. Several transcription start sites were identified within IGF-I exons 1 and 2, adjacent to presumptive promoters 1 and 2, respectively, and at least three polyadenylation sites were mapped to exon 6. To test promoter function, fusion genes were constructed linking fragments of IGF-I DNA to a reporter plasmid. Chimeric genes containing at least 395 bp of DNA from the 5'- flanking region of exon 1 enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line, while fusion plasmids containing up to 1,300 bp of DNA from the 5'-flanking region of exon 2 were inactive. Relative levels of IGF-I mRNAs containing exons 1 or 2 varied among different rat tissues, although in response to acute or chronic growth hormone treatment both classes of transcripts were induced coordinately in rat liver. These observations represent the first thorough characterization of a mammalian IGF-I gene, and provide a starting point for defining the mechanisms by which growth hormone and other trophic factors regulate IGF-I gene expression.

Original languageEnglish (US)
Pages (from-to)301-313
Number of pages13
JournalDNA and Cell Biology
Volume11
Issue number4
StatePublished - 1992
Externally publishedYes

Fingerprint

Insulin-Like Growth Factor I
Exons
Genes
Growth Hormone
5' Flanking Region
DNA
Messenger RNA
Plasmids
Gene Expression
Polyadenylation
Protein Precursors
Transcription Initiation Site
Gene Fusion
Growth
Luciferases
Transfection
Mammals
Cell Line
Liver

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Hall, L. J., Kajimoto, Y., Bichell, D., Kim, S. W., James, P. L., Counts, D., ... Rotwein, P. (1992). Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter. DNA and Cell Biology, 11(4), 301-313.

Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter. / Hall, L. J.; Kajimoto, Y.; Bichell, D.; Kim, S. W.; James, P. L.; Counts, D.; Nixon, L. J.; Tobin, G.; Rotwein, P.

In: DNA and Cell Biology, Vol. 11, No. 4, 1992, p. 301-313.

Research output: Contribution to journalArticle

Hall, LJ, Kajimoto, Y, Bichell, D, Kim, SW, James, PL, Counts, D, Nixon, LJ, Tobin, G & Rotwein, P 1992, 'Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter', DNA and Cell Biology, vol. 11, no. 4, pp. 301-313.
Hall LJ, Kajimoto Y, Bichell D, Kim SW, James PL, Counts D et al. Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter. DNA and Cell Biology. 1992;11(4):301-313.
Hall, L. J. ; Kajimoto, Y. ; Bichell, D. ; Kim, S. W. ; James, P. L. ; Counts, D. ; Nixon, L. J. ; Tobin, G. ; Rotwein, P. / Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter. In: DNA and Cell Biology. 1992 ; Vol. 11, No. 4. pp. 301-313.
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