Identification of multiple transcription start sites in the human insulin-like growth factor-I gene.
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.
Jansen
E
E
Laboratory for Physiological Chemistry, State University of Utrecht, The Netherlands.
Steenbergh
P H
PH
LeRoith
D
D
Roberts
C T
CT
Sussenbach
J S
JS
D001483:Base Sequence; D005091:Exons; D005260:Female; D005796:Genes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D007889:Leiomyoma / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014594:Uterine Neoplasms / Q000378:metabolism
D009363:Neoplasm Proteins; D007334:Insulin-Like Growth Factor I