Abstract
Insulin-like growth factor I (IGF-I) is a potent regulator of postnatal growth in mammals, yet little is known about the developmental control of IGF-I synthesis. We have investigated the regulation of IGF-I expression in the rat in order to gain insight into the mechanisms of growth factor induction during early postnatal life. Steady-state levels of liver IGF-I mRNA increased by more than 15-fold during the period from fetal day 18 to postnatal day 7 and reached 50% of adult values by day 14. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA each demonstrated a comparable rise in nascent IGF-I mRNA over the same time period. Over 90% of transcripts were directed by promoter 1, the more 5′ of the two IGF-I gene promoters. By contrast IGF-II gene transcription rates and mRNA levels fell during the first 3 weeks after birth, and albumin expression rose slightly. Analysis of chromatin structure around the IGF-I gene revealed 15 DNase I-hypersensitive sites in adult rat liver in the 120 kilobases (kb) comprising the 6 exon gene and its flanking regions (8 sites within 10 kb at the 5′-end including exons 1-3, 5 sites in the 50-kb third intron, and 2 sites in the 15-kb fifth intron). During development there was a progressive appearance of DNase I-hypersensitive sites that coincided with activation of IGF-I gene expression. One site that became fully hypersensitive by postnatal day 7 was mapped by in vivo DNAse I footprinting to the proximal 200 nucleotides of promoter 1. Since serum IGF-I values rose from 10 to 120 μg/liter during the initial postnatal week, these results indicate that transcriptional mechanisms are principally responsible for the stimulation of IGF-I synthesis that occurs shortly after birth. Because discrete changes in chromatin organization coincided with induction of IGF-I gene transcription, it is likely that a series of developmentally modulated transcription factors are involved the activation process.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 21505-21511 |
| Number of pages | 7 |
| Journal | Journal of Biological Chemistry |
| Volume | 267 |
| Issue number | 30 |
| State | Published - Oct 25 1992 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription. / Kikuchi, Kiyoshi; Bichell, David P.; Rotwein, Peter.
In: Journal of Biological Chemistry, Vol. 267, No. 30, 25.10.1992, p. 21505-21511.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription
AU - Kikuchi, Kiyoshi
AU - Bichell, David P.
AU - Rotwein, Peter
PY - 1992/10/25
Y1 - 1992/10/25
N2 - Insulin-like growth factor I (IGF-I) is a potent regulator of postnatal growth in mammals, yet little is known about the developmental control of IGF-I synthesis. We have investigated the regulation of IGF-I expression in the rat in order to gain insight into the mechanisms of growth factor induction during early postnatal life. Steady-state levels of liver IGF-I mRNA increased by more than 15-fold during the period from fetal day 18 to postnatal day 7 and reached 50% of adult values by day 14. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA each demonstrated a comparable rise in nascent IGF-I mRNA over the same time period. Over 90% of transcripts were directed by promoter 1, the more 5′ of the two IGF-I gene promoters. By contrast IGF-II gene transcription rates and mRNA levels fell during the first 3 weeks after birth, and albumin expression rose slightly. Analysis of chromatin structure around the IGF-I gene revealed 15 DNase I-hypersensitive sites in adult rat liver in the 120 kilobases (kb) comprising the 6 exon gene and its flanking regions (8 sites within 10 kb at the 5′-end including exons 1-3, 5 sites in the 50-kb third intron, and 2 sites in the 15-kb fifth intron). During development there was a progressive appearance of DNase I-hypersensitive sites that coincided with activation of IGF-I gene expression. One site that became fully hypersensitive by postnatal day 7 was mapped by in vivo DNAse I footprinting to the proximal 200 nucleotides of promoter 1. Since serum IGF-I values rose from 10 to 120 μg/liter during the initial postnatal week, these results indicate that transcriptional mechanisms are principally responsible for the stimulation of IGF-I synthesis that occurs shortly after birth. Because discrete changes in chromatin organization coincided with induction of IGF-I gene transcription, it is likely that a series of developmentally modulated transcription factors are involved the activation process.
AB - Insulin-like growth factor I (IGF-I) is a potent regulator of postnatal growth in mammals, yet little is known about the developmental control of IGF-I synthesis. We have investigated the regulation of IGF-I expression in the rat in order to gain insight into the mechanisms of growth factor induction during early postnatal life. Steady-state levels of liver IGF-I mRNA increased by more than 15-fold during the period from fetal day 18 to postnatal day 7 and reached 50% of adult values by day 14. Transcription run-on experiments using isolated hepatic nuclei and direct analysis of nuclear RNA each demonstrated a comparable rise in nascent IGF-I mRNA over the same time period. Over 90% of transcripts were directed by promoter 1, the more 5′ of the two IGF-I gene promoters. By contrast IGF-II gene transcription rates and mRNA levels fell during the first 3 weeks after birth, and albumin expression rose slightly. Analysis of chromatin structure around the IGF-I gene revealed 15 DNase I-hypersensitive sites in adult rat liver in the 120 kilobases (kb) comprising the 6 exon gene and its flanking regions (8 sites within 10 kb at the 5′-end including exons 1-3, 5 sites in the 50-kb third intron, and 2 sites in the 15-kb fifth intron). During development there was a progressive appearance of DNase I-hypersensitive sites that coincided with activation of IGF-I gene expression. One site that became fully hypersensitive by postnatal day 7 was mapped by in vivo DNAse I footprinting to the proximal 200 nucleotides of promoter 1. Since serum IGF-I values rose from 10 to 120 μg/liter during the initial postnatal week, these results indicate that transcriptional mechanisms are principally responsible for the stimulation of IGF-I synthesis that occurs shortly after birth. Because discrete changes in chromatin organization coincided with induction of IGF-I gene transcription, it is likely that a series of developmentally modulated transcription factors are involved the activation process.
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M3 - Article
C2 - 1400462
AN - SCOPUS:0026801525
VL - 267
SP - 21505
EP - 21511
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 30
ER -