Identification of multiple transcription start sites in the human insulin-like growth factor-I gene

E. Jansen, P. H. Steenbergh, D. LeRoith, C. T. Roberts, J. S. Sussenbach

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    80 Scopus citations

    Abstract

    We have localized four transcription initiation sites in the human insulin-like growth factor-I (IGF-I) gene. Two transcription start sites were identified which result in a longer and shorter version of the leader derived from the known exon 1 of the IGF-I gene. Transcription starting at the upstream transcription initiation site results in a leader exon 1 of about 1155 nucleotides (nt), whereas transcription starting at the downstream initiation site results in a leader of about 240 nt. The majority of the transcripts initiate at the latter site. We further identified a region in the human IGF-I gene between exons 1 and 2, which shows a high degree of homology with the rat IGF-I leader exon 1B. By means of the polymerase chain reaction (PCR) we detected human IGF-I mRNAs containing this novel leader. The corresponding exon was designated exon 1B according to the rat IGF-I gene terminology. PCR and RNase protection analyses identified two transcription start sites within this alternative leader exon 1B. Transcription initiated at the most upstream start site results in a leader of about 750 nt, whereas transcription starting at the downstream site is heterogeneous, resulting in leaders of 65-75 nt long. No consensus TATA-box or AT-rich regions are present immediately upstream of all four transcription start sites identified, nor are these regions particularly GC-rich. The IGF-I gene is known to be expressed differentially in a tissue- and development-specific fashion. Differential activation of multiple promoters could very well play a crucial role in IGF-I gene regulation.

    Original languageEnglish (US)
    Pages (from-to)115-125
    Number of pages11
    JournalMolecular and Cellular Endocrinology
    Volume78
    Issue number1-2
    DOIs
    StatePublished - Jun 1991

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    Keywords

    • Insulin-like growth factor-I
    • Leader exon
    • Polymerase chain reaction
    • RNase protection
    • Transcription start sites

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Endocrinology

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