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

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

Research output: Contribution to journalArticle

80 Citations (Scopus)

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 - 1991
Externally publishedYes

Fingerprint

Transcription Initiation Site
Insulin-Like Growth Factor I
Genes
Exons
Transcription
Nucleotides
Polymerase chain reaction
Rats
AT Rich Sequence
GC Rich Sequence
Polymerase Chain Reaction
TATA Box
Terminology
Ribonucleases
Gene expression
Chemical activation
Tissue
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Identification of multiple transcription start sites in the human insulin-like growth factor-I gene. / Jansen, E.; Steenbergh, P. H.; LeRoith, D.; Roberts, Charles; Sussenbach, J. S.

In: Molecular and Cellular Endocrinology, Vol. 78, No. 1-2, 1991, p. 115-125.

Research output: Contribution to journalArticle

Jansen, E. ; Steenbergh, P. H. ; LeRoith, D. ; Roberts, Charles ; Sussenbach, J. S. / Identification of multiple transcription start sites in the human insulin-like growth factor-I gene. In: Molecular and Cellular Endocrinology. 1991 ; Vol. 78, No. 1-2. pp. 115-125.
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