Transcription initiation in the two leader exons of the rat IGF-I gene occurs from disperse versus localized sites.
Rat IGF-I mRNAs contain two different 5'-UTR sequences as a result of alternate splicing of leader exons. Using a combination of solution hybridization/RNase protection and primer extension assays, we have mapped the transcriptional start sites in these leader exons. There appear to be three putative transcription start sites in exon 1 spread over a 140-bp region, the most upstream of which defines a 381 bp-long exon 1. There appear to be three distinct start sites in exon 2, the most upstream of which defines a greater than 770 bp-long exon 2. The two downstream start sites in exon 1 together account for approximately 70% of IGF-I gene expression in adult rat liver. Essentially all of the remaining IGF-I gene expression comes from the second start site in exon 2. Rat IGF-I gene transcription may therefore be regulated by two distinct promoter regions, a disperse promoter for exon 1, with several transcription initiation sites, and a more typical promoter region for exon 2, which controls transcription initiation from a discrete region.
Adamo
M L
ML
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Ben-Hur
H
H
LeRoith
D
D
Roberts
C T
CT
D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D005091:Exons; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000737:chemistry*; D051381:Rats; D015183:Restriction Mapping; D014158:Transcription, Genetic
D015342:DNA Probes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I