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Updated: Oct 19, 2026

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
08:54

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression

Published on: March 29, 2019

Repression and activation of transcription of phosphoenolpyruvate carboxykinase gene during liver development

H Cassuto1, A Aran, H Cohen

  • 1The Department of Developmental Biochemistry, Hebrew University-Hadassah Medical School, P.O. Box 12272, Jerusalem, Israel.

FEBS Letters
|September 3, 1999
PubMed

Insights

The hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • Hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene transcription is critical for initiating hepatic gluconeogenesis at birth.
  • Dysregulation of PEPCK expression leads to life-incompatible conditions like hypoglycemia or neonatal diabetes.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling the precise onset of hepatic PEPCK gene transcription.
  • To identify DNA sequences and transcription factors involved in PEPCK gene repression and activation.

Main Methods:

  • Utilized transgenic mice and transfected hepatoma cells (Hepa1c1c7) to study PEPCK promoter activity.
  • Analyzed promoter constructs of varying lengths (597 bp and 2000 bp) and specific DNA sequences.
  • Investigated the effects of transcription factors like HNF-1, C/EBP, RXRalpha, and PPARalpha on PEPCK gene expression.

Main Results:

  • Transgenes driven by the PEPCK promoter showed premature and over-expression in fetal and neonatal mouse livers, respectively.
  • A 597 bp proximal promoter had higher activity than longer constructs in Hepa1c1c7 cells.
  • Deletion of a region containing a PPAR/RXR element reduced repression of a 2000 bp promoter.
  • HNF-1/C/EBP activated the promoter, while RXRalpha repressed it, an effect reversed by PPARalpha.

Conclusions:

  • Upstream sequences of the PEPCK gene play a crucial role in restraining perinatal expression.
  • Specific transcription factors and their interactions with regulatory elements dictate the precise transcriptional control of PEPCK.
  • Understanding these regulatory mechanisms is vital for comprehending metabolic adaptations at birth.

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