Estrogen-inducible derivatives of hepatocyte nuclear factor-4, hepatocyte nuclear factor-3 and liver factor B1 are

Related Experiment Video

Updated: Oct 6, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 16, 2013

T Drewes1, A Clairmont, L Klein-Hitpass

  • 1Institut für Zellbiologie, Universitätsklinikum Essen, Germany.

European Journal of Biochemistry
|October 1, 1994
PubMed

Insights

Researchers engineered novel transcription factors by fusing hepatocyte nuclear factor (HNF) proteins with the estrogen receptor. These fusion proteins offer new ways to study gene expression and development.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Endocrinology

Background:

  • Tissue-specific transcription factors like hepatocyte nuclear factor-4 (HNF4), hepatocyte nuclear factor-3 (HNF3), and liver factor B1 (LFB1) are crucial for organ development and gene regulation.
  • Understanding the precise roles of these factors in gene expression and developmental processes is essential.

Purpose of the Study:

  • To create novel, hormone-inducible transcription factors by fusing HNF proteins with the estrogen receptor's hormone-binding domain.
  • To investigate the functionality and response of these chimeric proteins to estrogen and anti-estrogens.

Main Methods:

  • Construction of chimeric transcription factors by introducing the estrogen receptor's hormone-binding domain into HNF4, HNF3, and LFB1.
  • Transient transfection assays to assess the activity of chimeric proteins.
  • Evaluation of the response of chimeric factors to estrogen, 4-hydroxytamoxifen, and ICI 164384.

Main Results:

  • Chimeric proteins function as estrogen-inducible transcription factors, retaining the DNA-binding specificity of the original HNF factors.
  • Differential responses to anti-estrogens were observed: 4-hydroxytamoxifen activated all chimeric factors, while ICI 164384 activated HNF3 and LFB1 derivatives but inhibited HNF4 and estrogen receptor.
  • The DNA-binding specificity and distinct hormonal responses were characterized.

Conclusions:

  • Estrogen receptor fusion proteins serve as valuable tools for studying the roles of HNF4, HNF3, and LFB1 in gene expression, differentiation, and development.
  • The differential sensitivity to estrogen and anti-estrogens provides a means to dissect the functions of these transcription factors.
  • These engineered factors enable precise investigation into complex biological processes regulated by HNF proteins.

More Related Videos

Stabilizing Hepatocellular Phenotype Using Optimized Synthetic Surfaces08:50

Stabilizing Hepatocellular Phenotype Using Optimized Synthetic Surfaces

Published on: September 26, 2014

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug binding...
Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug01:14

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...