Related Experiment Video

Updated: Oct 10, 2026

Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction
10:46

Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction

Published on: November 3, 2011

COUP-TF1 antagonizes Nkx2.5-mediated activation of the calreticulin gene during cardiac development

L Guo1, J Lynch, K Nakamura

  • 1Canadian Institutes of Health Research Group in Molecular Biology of Membrane Proteins, University of Alberta, Edmonton, Alberta, Canada.

The Journal of Biological Chemistry
|December 7, 2000
PubMed

Insights

The transcription factor Nkx2.5 activates calreticulin gene expression crucial for embryonic heart development. Antagonistic roles of Nkx2.5 and chicken ovalbumin upstream promoter-transcription factor 1 regulate calreticulin during cardiac development.

Area of Science:

  • Molecular Biology
  • Cardiovascular Biology
  • Developmental Biology

Background:

  • Calreticulin (CRT) is a Ca(2+) binding chaperone in the endoplasmic reticulum.
  • High CRT expression is vital for embryonic heart development; its absence is embryonically lethal.
  • Down-regulated postnatally, elevated CRT in newborn hearts correlates with severe cardiac pathology.

Purpose of the Study:

  • To investigate the transcriptional regulation of the calreticulin gene in the heart.
  • To elucidate the roles of transcription factors Nkx2.5 and chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1) in cardiac calreticulin expression.

Main Methods:

  • Analysis of calreticulin gene promoter activity.
  • Investigation of transcription factor binding and their effects on gene expression.
  • Study of antagonistic interactions between Nkx2.5 and COUP-TF1.

Main Results:

  • The cardiac-specific transcription factor Nkx2.5 directly activates calreticulin gene expression.
  • Binding of COUP-TF1 to the Nkx2.5 binding site on the calreticulin promoter suppresses transcription.
  • Nkx2.5 and COUP-TF1 exhibit antagonistic functions in regulating cardiac calreticulin.

Conclusions:

  • Nkx2.5 plays a pivotal role in activating cardiac calreticulin expression during development.
  • Cooperative and antagonistic interactions between Nkx2.5 and COUP-TF1 at the calreticulin promoter are critical for cardiac development.

More Related Videos

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter05:04

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter

Published on: February 22, 2022

Related Concept Videos

Enzyme-linked Receptors01:13

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...