Related Experiment Video

Updated: Aug 8, 2026

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
07:23

Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome

Published on: June 15, 2016

v-Jun downregulates the SPARC target gene by binding to the proximal promoter indirectly through Sp1/3

Sandrine Chamboredon1, Joseph Briggs, Emmanuel Vial

  • 1Unité de Virologie Humaine, INSERM-U412, Ecole Normale Supérieure, 46 allée d'ltalie, 69364 Lyon cedex 07, France.

Oncogene
|June 25, 2003
PubMed

Insights

The v-Jun oncoprotein downregulates SPARC by forming a complex with Sp1/3 transcription factors. This interaction represses SPARC gene expression, contributing to tumor development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • The v-Jun oncoprotein is known to transform cells and affect gene expression.
  • SPARC (Secreted Protein Acidic and Rich in Cysteine) is an extracellular matrix protein implicated in tumor development.
  • The SPARC gene promoter (-124/+16) is crucial for its high activity and is targeted by v-Jun.

Purpose of the Study:

  • To elucidate the mechanism by which v-Jun downregulates SPARC expression.
  • To determine the role of Sp1 and Sp3 transcription factors in SPARC gene regulation.
  • To investigate the direct or indirect binding of v-Jun to the SPARC promoter.

Main Methods:

  • Electrophoretic mobility shift assays (EMSA) and pull-down assays.
  • Transient transfection assays in Sp1/3-deficient Drosophila SL2 cells and chick embryo fibroblasts.
  • Chromatin immunoprecipitation (ChIP) assays.

Main Results:

  • Sp1 and/or Sp3 directly bind to the -92/-57 fragment of the SPARC promoter, activating transcription.
  • v-Jun does not directly bind the SPARC promoter but interacts indirectly with Sp1/3.
  • A modified v-Jun derivative, v-Jun/cebp/glz, efficiently downregulates SPARC without direct DNA binding, suggesting a protein-protein interaction mechanism.

Conclusions:

  • v-Jun downregulates SPARC transcription indirectly through physical interaction with Sp1/3.
  • The formation of a DNA-Sp1/3-v-Jun chromatin-associated complex is the likely mechanism for SPARC repression.
  • This repression mechanism contributes to the oncogenic potential of v-Jun by facilitating tumor development.

More Related Videos

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins11:34

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins

Published on: August 9, 2019

Related Concept Videos

Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...