Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Transcription Factors02:16

Transcription Factors

70.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
70.8K
Transcription Factors02:16

Transcription Factors

21.7K
21.7K
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

8.9K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
8.9K
Conserved Binding Sites01:49

Conserved Binding Sites

4.1K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.1K
Conserved Binding Sites01:49

Conserved Binding Sites

1.1K
1.1K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

7.0K
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...
7.0K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Developing Future Biologists: developmental biology for undergraduates from underserved communities.

Development (Cambridge, England)·2023
Same author

Defending harassers harms victims.

Science (New York, N.Y.)·2019
Same author

How to tune an enhancer.

Proceedings of the National Academy of Sciences of the United States of America·2016
Same author

An ancient yet flexible cis-regulatory architecture allows localized Hedgehog tuning by patched/Ptch1.

eLife·2016
Same author

Identification and Validation of Novel Hedgehog-Responsive Enhancers Predicted by Computational Analysis of Ci/Gli Binding Site Density.

PloS one·2015
Same author

Enhancers: holding out for the right promoter.

Current biology : CB·2015

Related Experiment Video

Updated: May 6, 2026

Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
11:36

Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations

Published on: April 21, 2023

2.7K

Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution.

Andrea I Ramos1, Scott Barolo

  • 1Department of Cell and Developmental Biology and Program in Cellular and Molecular Biology, University of Michigan Medical School, , Ann Arbor, MI 48109, USA.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
|November 13, 2013
PubMed
Summary
This summary is machine-generated.

Low-affinity transcription factor binding sites are crucial for activating genes in response to Hedgehog signaling gradients. Enhancing binding affinity disrupts normal gene activation, leading to developmental defects.

Keywords:
Ci/Glibinding affinityenhancersgene regulationhedgehog signallingmorphogen gradient

More Related Videos

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA
07:05

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA

Published on: September 8, 2021

2.1K
High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
06:38

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

Published on: February 7, 2019

10.7K

Related Experiment Videos

Last Updated: May 6, 2026

Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
11:36

Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations

Published on: April 21, 2023

2.7K
Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA
07:05

Single-Molecule Imaging of EWS-FLI1 Condensates Assembling on DNA

Published on: September 8, 2021

2.1K
High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy
06:38

High Sensitivity Measurement of Transcription Factor-DNA Binding Affinities by Competitive Titration Using Fluorescence Microscopy

Published on: February 7, 2019

10.7K

Area of Science:

  • Developmental Biology
  • Genomics
  • Molecular Biology

Background:

  • Transcription factor (TF)-DNA binding affinity is increasingly studied in functional genomics.
  • The functional relevance of low-affinity TF binding events is debated.
  • Hedgehog (Hh) signaling gradients are critical for development, transduced by the Ci (Gli family) TF in Drosophila.

Purpose of the Study:

  • To investigate the role of binding site affinity in the transcriptional interpretation of Hh morphogen gradients.
  • To understand how Ci/Gli binding affinity influences the activation and repression of Hh-responsive genes.

Main Methods:

  • Analysis of low predicted Ci/Gli binding affinity in enhancers of Hh-responsive Drosophila genes (dpp, wingless, stripe).
  • Experimental manipulation of Ci/Gli binding site affinity in endogenous enhancers and synthetic reporters.
  • Assessment of transcriptional responses and patterning defects in Drosophila imaginal discs.

Main Results:

  • Improving Ci/Gli binding site affinity did not cause ectopic Hh signaling responses.
  • Hh-responsive enhancers require low-affinity binding sites for normal activation in low signaling regions.
  • Altering Ci/Gli sites to higher affinity caused patterning defects, indicating a switch from activation to repression.

Conclusions:

  • Low-affinity binding sites are essential for gene activation by Ci in moderate Hh signaling environments.
  • Evolutionary pressure favors weak binding sites in enhancers of certain Hh target genes.
  • Binding site affinity is a critical determinant of TF function in morphogen gradient interpretation.