Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription

Kiyoshi Kikuchi, David P. Bichell, Peter Rotwein

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)21505-21511
Number of pages7
JournalJournal of Biological Chemistry
Volume267
Issue number30
StatePublished - Oct 25 1992
Externally publishedYes

Fingerprint

Transcription
Insulin-Like Growth Factor I
Chromatin
Genes
Chemical activation
Deoxyribonuclease I
Liver
Introns
Messenger RNA
Rats
Exons
Parturition
Nuclear RNA
Insulin-Like Growth Factor II
Mammals
Gene expression
Albumins
Intercellular Signaling Peptides and Proteins
Transcription Factors
Nucleotides

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 journalArticle

Kikuchi, Kiyoshi ; Bichell, David P. ; Rotwein, Peter. / Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 30. pp. 21505-21511.
@article{aee139224681459aac06f75aa4999e2c,
title = "Chromatin changes accompany the developmental activation of insulin-like growth factor I gene transcription",
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.",
author = "Kiyoshi Kikuchi and Bichell, {David P.} and Peter Rotwein",
year = "1992",
month = "10",
day = "25",
language = "English (US)",
volume = "267",
pages = "21505--21511",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "30",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=0026801525&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026801525&partnerID=8YFLogxK

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 -