Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4

Inhibition by cyclic AMP and COUP transcription factors

Min You, Monika Fischer, David Crabb, Kyoo Cho Won

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

An important regulatory element (designated FP330-3′) of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARδ suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3′ by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3′. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume398
Issue number1
DOIs
StatePublished - Feb 1 2002

Fingerprint

COUP Transcription Factors
Hepatocyte Nuclear Factor 4
Aldehyde Dehydrogenase
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Assays
Fasting
Chemical activation
Electrophoretic mobility
Peroxisome Proliferator-Activated Receptors
Aptitude
Electrophoretic Mobility Shift Assay
Inhibition (Psychology)
Glucagon
Liver
Rats
Hepatocytes
Hepatocellular Carcinoma
Cultured Cells

Keywords

  • COUP transcription factors, fasting
  • Cyclic AMP
  • Hepatocyte nuclear factor 4
  • Human aldehyde dehydrogenase 2 promoter

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

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title = "Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: Inhibition by cyclic AMP and COUP transcription factors",
abstract = "An important regulatory element (designated FP330-3′) of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARδ suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3′ by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3′. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.",
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T1 - Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4

T2 - Inhibition by cyclic AMP and COUP transcription factors

AU - You, Min

AU - Fischer, Monika

AU - Crabb, David

AU - Won, Kyoo Cho

PY - 2002/2/1

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N2 - An important regulatory element (designated FP330-3′) of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARδ suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3′ by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3′. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.

AB - An important regulatory element (designated FP330-3′) of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARδ suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3′ by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3′. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.

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KW - Hepatocyte nuclear factor 4

KW - Human aldehyde dehydrogenase 2 promoter

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