Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter

Kuang Ming Hsiao, Stephanie L. McMahon, Peggy J. Farnham

Research output: Contribution to journalArticle

216 Citations (Scopus)

Abstract

To prepare for the DNA synthesis (S) phase of the cell cycle, transcription of many genes required for nucleotide biosynthesis increases. The promoters of several of these genes contain binding sites for the E2F family of transcription factors, and, in many cases, mutation of these sites abolishes growth-regulated transcription. The RNA levels of one family member, E2F1, increase about 15-fold at the G1/S-phase boundary and expression of E2F1 in quiescent cells activates transcription from some G1/S-phase-specific promoters, suggesting that E2F1 plays a critical role in preparing cells to enter S phase. To elucidate the signal transduction pathway leading to the activation of genes required for DNA synthesis, we are investigating the mechanism by which expression of E2F1 is regulated. To determine whether levels of E2F1 mRNA are controlled by changes in promoter activity, we have cloned and characterized the mouse E2F1 promoter. Sequence analysis revealed two sets of overlapping E2F-binding sites located between - 12 and -40 relative to the transcription initiation site. We show that these sites bind cellular E2F and that an E2F1 promoter fragment can be activated up to 100-fold by coexpression of E2F proteins. We also show that the activity of this E2F1 promoter fragment increases ~80-fold at the G1/S- phase boundary and that this activation is, in part, regulated by G0- specific repression via the E2F sites. However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary.

Original languageEnglish (US)
Pages (from-to)1526-1537
Number of pages12
JournalGenes and Development
Volume8
Issue number13
StatePublished - 1994
Externally publishedYes

Fingerprint

S Phase
G1 Phase
DNA
Growth
E2F Transcription Factors
Binding Sites
Transcription Initiation Site
Transcriptional Activation
Genes
Sequence Analysis
Signal Transduction
Cell Cycle
Nucleotides
RNA
Messenger RNA
Mutation

Keywords

  • cell cycle
  • E2F
  • growth regulation
  • promoter
  • transcription

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Hsiao, K. M., McMahon, S. L., & Farnham, P. J. (1994). Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes and Development, 8(13), 1526-1537.

Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. / Hsiao, Kuang Ming; McMahon, Stephanie L.; Farnham, Peggy J.

In: Genes and Development, Vol. 8, No. 13, 1994, p. 1526-1537.

Research output: Contribution to journalArticle

Hsiao, KM, McMahon, SL & Farnham, PJ 1994, 'Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter', Genes and Development, vol. 8, no. 13, pp. 1526-1537.
Hsiao, Kuang Ming ; McMahon, Stephanie L. ; Farnham, Peggy J. / Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. In: Genes and Development. 1994 ; Vol. 8, No. 13. pp. 1526-1537.
@article{5d6972a06a8141869bca7faa604c8324,
title = "Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter",
abstract = "To prepare for the DNA synthesis (S) phase of the cell cycle, transcription of many genes required for nucleotide biosynthesis increases. The promoters of several of these genes contain binding sites for the E2F family of transcription factors, and, in many cases, mutation of these sites abolishes growth-regulated transcription. The RNA levels of one family member, E2F1, increase about 15-fold at the G1/S-phase boundary and expression of E2F1 in quiescent cells activates transcription from some G1/S-phase-specific promoters, suggesting that E2F1 plays a critical role in preparing cells to enter S phase. To elucidate the signal transduction pathway leading to the activation of genes required for DNA synthesis, we are investigating the mechanism by which expression of E2F1 is regulated. To determine whether levels of E2F1 mRNA are controlled by changes in promoter activity, we have cloned and characterized the mouse E2F1 promoter. Sequence analysis revealed two sets of overlapping E2F-binding sites located between - 12 and -40 relative to the transcription initiation site. We show that these sites bind cellular E2F and that an E2F1 promoter fragment can be activated up to 100-fold by coexpression of E2F proteins. We also show that the activity of this E2F1 promoter fragment increases ~80-fold at the G1/S- phase boundary and that this activation is, in part, regulated by G0- specific repression via the E2F sites. However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary.",
keywords = "cell cycle, E2F, growth regulation, promoter, transcription",
author = "Hsiao, {Kuang Ming} and McMahon, {Stephanie L.} and Farnham, {Peggy J.}",
year = "1994",
language = "English (US)",
volume = "8",
pages = "1526--1537",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "13",

}

TY - JOUR

T1 - Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter

AU - Hsiao, Kuang Ming

AU - McMahon, Stephanie L.

AU - Farnham, Peggy J.

PY - 1994

Y1 - 1994

N2 - To prepare for the DNA synthesis (S) phase of the cell cycle, transcription of many genes required for nucleotide biosynthesis increases. The promoters of several of these genes contain binding sites for the E2F family of transcription factors, and, in many cases, mutation of these sites abolishes growth-regulated transcription. The RNA levels of one family member, E2F1, increase about 15-fold at the G1/S-phase boundary and expression of E2F1 in quiescent cells activates transcription from some G1/S-phase-specific promoters, suggesting that E2F1 plays a critical role in preparing cells to enter S phase. To elucidate the signal transduction pathway leading to the activation of genes required for DNA synthesis, we are investigating the mechanism by which expression of E2F1 is regulated. To determine whether levels of E2F1 mRNA are controlled by changes in promoter activity, we have cloned and characterized the mouse E2F1 promoter. Sequence analysis revealed two sets of overlapping E2F-binding sites located between - 12 and -40 relative to the transcription initiation site. We show that these sites bind cellular E2F and that an E2F1 promoter fragment can be activated up to 100-fold by coexpression of E2F proteins. We also show that the activity of this E2F1 promoter fragment increases ~80-fold at the G1/S- phase boundary and that this activation is, in part, regulated by G0- specific repression via the E2F sites. However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary.

AB - To prepare for the DNA synthesis (S) phase of the cell cycle, transcription of many genes required for nucleotide biosynthesis increases. The promoters of several of these genes contain binding sites for the E2F family of transcription factors, and, in many cases, mutation of these sites abolishes growth-regulated transcription. The RNA levels of one family member, E2F1, increase about 15-fold at the G1/S-phase boundary and expression of E2F1 in quiescent cells activates transcription from some G1/S-phase-specific promoters, suggesting that E2F1 plays a critical role in preparing cells to enter S phase. To elucidate the signal transduction pathway leading to the activation of genes required for DNA synthesis, we are investigating the mechanism by which expression of E2F1 is regulated. To determine whether levels of E2F1 mRNA are controlled by changes in promoter activity, we have cloned and characterized the mouse E2F1 promoter. Sequence analysis revealed two sets of overlapping E2F-binding sites located between - 12 and -40 relative to the transcription initiation site. We show that these sites bind cellular E2F and that an E2F1 promoter fragment can be activated up to 100-fold by coexpression of E2F proteins. We also show that the activity of this E2F1 promoter fragment increases ~80-fold at the G1/S- phase boundary and that this activation is, in part, regulated by G0- specific repression via the E2F sites. However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary.

KW - cell cycle

KW - E2F

KW - growth regulation

KW - promoter

KW - transcription

UR - http://www.scopus.com/inward/record.url?scp=0028276864&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028276864&partnerID=8YFLogxK

M3 - Article

VL - 8

SP - 1526

EP - 1537

JO - Genes and Development

JF - Genes and Development

SN - 0890-9369

IS - 13

ER -