Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation

Yuan Xiang Pan, Hong Chen, Michelle M. Thiaville, Michael S. Kilberg

Research output: Contribution to journalArticle

Abstract

Expression of ATF3 (activating transcription factor 3) is induced by a variety of environmental stress conditions, including nutrient limitation. In the present study, we demonstrate that the increase in ATF3 mRNA content following amino acid limitation of human HepG2 hepatoma cells is dependent on transcriptional activation of the ATF3 gene, through a highly coordinated amino acid-responsive programme of transcription factor synthesis and action. Studies using transient overexpression and knockout fibroblasts showed that several ATF and C/EBP (CCAAT/enhancer-binding protein) family members contribute to ATF3 regulation. Promoter analysis showed that a C/EBP-ATF composite site at -23 to -15 bp relative to the transcription start site of the ATF3 gene functions as an AARE (amino acid response element). Chromatin immunoprecipitation demonstrated that amino acid limitation increased ATF4, ATF3, and C/EBPβ binding to the ATF3 promoter, but the kinetics of each was markedly different. Immediately following histidine removal, there was a rapid increase in histone H3 acetylation prior to an enhancement in ATF4 binding and in histone H4 acetylation. These latter changes closely paralleled the initial increase in RNA pol II (RNA polymerase II) binding to the promoter and in the transcription rate from the ATF3 gene. The increase in ATF3 and C/EBPβ binding was considerably slower and more closely correlated with a decline in transcription rate. A comparison of the recruitment patterns between ATF and C/EBP transcription factors and RNA polymerase II at the AARE of several amino acid-responsive genes revealed that a highly co-ordinated response programme controls the transcriptional activation of these genes following amino acid limitation.

Original languageEnglish (US)
Pages (from-to)299-307
Number of pages9
JournalBiochemical Journal
Volume401
Issue number1
DOIs
StatePublished - Jan 1 2007
Externally publishedYes

Fingerprint

Activating Transcription Factor 3
CCAAT-Enhancer-Binding Proteins
Genes
Chemical activation
Amino Acids
RNA Polymerase II
Acetylation
Response Elements
Transcription
Protein Binding
Histones
Transcriptional Activation
Activating Transcription Factor 4
Transcription Factors
Chromatin Immunoprecipitation
Transcription Initiation Site
Hep G2 Cells
Fibroblasts
Histidine
Nutrients

Keywords

  • Activating transcription factor 3 (ATF3)
  • Amino acid response element (AARE)
  • Amino acid-sensing
  • CCAAT/enhancer-binding protein (C/EBP)
  • Histone acetylation
  • Transcription regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

@article{aa9bacbde9cb4a68abcc1bb8b5138bd6,
title = "Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation",
abstract = "Expression of ATF3 (activating transcription factor 3) is induced by a variety of environmental stress conditions, including nutrient limitation. In the present study, we demonstrate that the increase in ATF3 mRNA content following amino acid limitation of human HepG2 hepatoma cells is dependent on transcriptional activation of the ATF3 gene, through a highly coordinated amino acid-responsive programme of transcription factor synthesis and action. Studies using transient overexpression and knockout fibroblasts showed that several ATF and C/EBP (CCAAT/enhancer-binding protein) family members contribute to ATF3 regulation. Promoter analysis showed that a C/EBP-ATF composite site at -23 to -15 bp relative to the transcription start site of the ATF3 gene functions as an AARE (amino acid response element). Chromatin immunoprecipitation demonstrated that amino acid limitation increased ATF4, ATF3, and C/EBPβ binding to the ATF3 promoter, but the kinetics of each was markedly different. Immediately following histidine removal, there was a rapid increase in histone H3 acetylation prior to an enhancement in ATF4 binding and in histone H4 acetylation. These latter changes closely paralleled the initial increase in RNA pol II (RNA polymerase II) binding to the promoter and in the transcription rate from the ATF3 gene. The increase in ATF3 and C/EBPβ binding was considerably slower and more closely correlated with a decline in transcription rate. A comparison of the recruitment patterns between ATF and C/EBP transcription factors and RNA polymerase II at the AARE of several amino acid-responsive genes revealed that a highly co-ordinated response programme controls the transcriptional activation of these genes following amino acid limitation.",
keywords = "Activating transcription factor 3 (ATF3), Amino acid response element (AARE), Amino acid-sensing, CCAAT/enhancer-binding protein (C/EBP), Histone acetylation, Transcription regulation",
author = "Pan, {Yuan Xiang} and Hong Chen and Thiaville, {Michelle M.} and Kilberg, {Michael S.}",
year = "2007",
month = "1",
day = "1",
doi = "10.1042/BJ20061261",
language = "English (US)",
volume = "401",
pages = "299--307",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

TY - JOUR

T1 - Activation of the ATF3 gene through a co-ordinated amino acid-sensing response programme that controls transcriptional regulation of responsive genes following amino acid limitation

AU - Pan, Yuan Xiang

AU - Chen, Hong

AU - Thiaville, Michelle M.

AU - Kilberg, Michael S.

PY - 2007/1/1

Y1 - 2007/1/1

N2 - Expression of ATF3 (activating transcription factor 3) is induced by a variety of environmental stress conditions, including nutrient limitation. In the present study, we demonstrate that the increase in ATF3 mRNA content following amino acid limitation of human HepG2 hepatoma cells is dependent on transcriptional activation of the ATF3 gene, through a highly coordinated amino acid-responsive programme of transcription factor synthesis and action. Studies using transient overexpression and knockout fibroblasts showed that several ATF and C/EBP (CCAAT/enhancer-binding protein) family members contribute to ATF3 regulation. Promoter analysis showed that a C/EBP-ATF composite site at -23 to -15 bp relative to the transcription start site of the ATF3 gene functions as an AARE (amino acid response element). Chromatin immunoprecipitation demonstrated that amino acid limitation increased ATF4, ATF3, and C/EBPβ binding to the ATF3 promoter, but the kinetics of each was markedly different. Immediately following histidine removal, there was a rapid increase in histone H3 acetylation prior to an enhancement in ATF4 binding and in histone H4 acetylation. These latter changes closely paralleled the initial increase in RNA pol II (RNA polymerase II) binding to the promoter and in the transcription rate from the ATF3 gene. The increase in ATF3 and C/EBPβ binding was considerably slower and more closely correlated with a decline in transcription rate. A comparison of the recruitment patterns between ATF and C/EBP transcription factors and RNA polymerase II at the AARE of several amino acid-responsive genes revealed that a highly co-ordinated response programme controls the transcriptional activation of these genes following amino acid limitation.

AB - Expression of ATF3 (activating transcription factor 3) is induced by a variety of environmental stress conditions, including nutrient limitation. In the present study, we demonstrate that the increase in ATF3 mRNA content following amino acid limitation of human HepG2 hepatoma cells is dependent on transcriptional activation of the ATF3 gene, through a highly coordinated amino acid-responsive programme of transcription factor synthesis and action. Studies using transient overexpression and knockout fibroblasts showed that several ATF and C/EBP (CCAAT/enhancer-binding protein) family members contribute to ATF3 regulation. Promoter analysis showed that a C/EBP-ATF composite site at -23 to -15 bp relative to the transcription start site of the ATF3 gene functions as an AARE (amino acid response element). Chromatin immunoprecipitation demonstrated that amino acid limitation increased ATF4, ATF3, and C/EBPβ binding to the ATF3 promoter, but the kinetics of each was markedly different. Immediately following histidine removal, there was a rapid increase in histone H3 acetylation prior to an enhancement in ATF4 binding and in histone H4 acetylation. These latter changes closely paralleled the initial increase in RNA pol II (RNA polymerase II) binding to the promoter and in the transcription rate from the ATF3 gene. The increase in ATF3 and C/EBPβ binding was considerably slower and more closely correlated with a decline in transcription rate. A comparison of the recruitment patterns between ATF and C/EBP transcription factors and RNA polymerase II at the AARE of several amino acid-responsive genes revealed that a highly co-ordinated response programme controls the transcriptional activation of these genes following amino acid limitation.

KW - Activating transcription factor 3 (ATF3)

KW - Amino acid response element (AARE)

KW - Amino acid-sensing

KW - CCAAT/enhancer-binding protein (C/EBP)

KW - Histone acetylation

KW - Transcription regulation

UR - http://www.scopus.com/inward/record.url?scp=33846277296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846277296&partnerID=8YFLogxK

U2 - 10.1042/BJ20061261

DO - 10.1042/BJ20061261

M3 - Article

C2 - 16989641

AN - SCOPUS:33846277296

VL - 401

SP - 299

EP - 307

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -