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Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form dimers that...
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...
Cis-regulatory Sequences02:02

Cis-regulatory Sequences

Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
Conserved Binding Sites01:49

Conserved Binding Sites

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 analyses the...
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

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A Reverse Genetic Approach to Test Functional Redundancy During Embryogenesis
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A Reverse Genetic Approach to Test Functional Redundancy During Embryogenesis

Published on: August 11, 2010

Backup in gene regulatory networks explains differences between binding and knockout results.

Anthony Gitter1, Zehava Siegfried, Michael Klutstein

  • 1Computer Science Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.

Molecular Systems Biology
|June 19, 2009
PubMed
Summary

Redundant transcription factors (TFs) explain why gene binding doesn't always change gene expression after a knockout. Considering cellular context reveals that TF binding is largely functional, highlighting biological system robustness.

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Area of Science:

  • Systems biology
  • Genomics
  • Molecular biology

Background:

  • Gene expression and protein-DNA interaction data have successfully modeled biological systems.
  • Recent studies question the direct relationship between transcription factor (TF) binding and gene expression changes upon TF knockout.
  • A majority of TF-bound genes show no significant expression change after TF knockout, challenging existing models.

Purpose of the Study:

  • To investigate the reasons behind the weak correlation between TF binding and gene expression changes post-knockout.
  • To explore the role of cellular context, including TF redundancy and protein interaction networks, in explaining these discrepancies.
  • To re-evaluate the functional significance of TF binding in biological systems.

Main Methods:

  • Analysis of gene expression and protein-DNA interaction data across multiple species.
  • Assessment of TF functional redundancy using paralog analysis.
  • Integration of protein-protein interaction networks to understand knockout effects.
  • Performance of new double knockout experiments to validate findings.

Main Results:

  • The agreement between TF binding and target gene expression increases fourfold when functional redundancy is absent.
  • Protein interaction networks provide mechanistic explanations for observed knockout effects.
  • Double knockout experiments confirm the influence of redundancy and network context.

Conclusions:

  • TF redundancy contributes to the robustness of biological systems by buffering against knockout effects.
  • Incorporating cellular context, such as protein interaction networks, is crucial for accurately interpreting TF binding data.
  • Despite apparent discrepancies, TF binding remains largely functional within the broader cellular environment.