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Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

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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...
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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...
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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...
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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...
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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...
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Updated: Jul 23, 2025

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Ultra-long-range interactions between active regulatory elements.

Elias T Friman1, Ilya M Flyamer2, Davide Marenduzzo3

  • 1MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom; Elias.Friman@ed.ac.uk Wendy.Bickmore@ed.ac.uk.

Genome Research
|July 14, 2023
PubMed
Summary
This summary is machine-generated.

Active regulatory elements interact across vast genomic distances, driven by multivalent binding factors and distinct processes like cohesin-mediated loop extrusion, polycomb contacts, and active region clustering. This clarifies gene regulation mechanisms.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Gene Regulation

Background:

  • Chromatin interactions between enhancers and promoters are crucial for gene transcription activation.
  • Understanding the factors driving these interactions is key to deciphering gene regulation.

Purpose of the Study:

  • To investigate the factors contributing to chromatin interactions between cis-regulatory elements.
  • To analyze contact frequencies and DNA-binding factor association with these interactions across large genomic distances.

Main Methods:

  • Utilized chromosome conformation capture (3C) data to determine contact frequencies between millions of cis-regulatory elements.
  • Analyzed binding of hundreds of DNA-binding factors at regions with enriched contacts.
  • Employed simulations to model chromatin interactions and multivalent binding factors.

Main Results:

  • Identified enriched contacts at sites bound by factors associated with active transcription.
  • Demonstrated that active regulatory elements interact across tens of megabases in diverse genomes, independent of cohesin and polycomb.
  • Showed these ultra-long-range interactions are not dependent on RNA polymerase II or individual transcription cofactors.
  • Simulations supported a model where multivalent binding factors drive long-range interactions via bridging-induced clustering.

Conclusions:

  • Long-range interactions between cis-regulatory elements are driven by multiple distinct processes.
  • These processes include cohesin-mediated loop extrusion, polycomb contacts, and clustering of active regions.
  • Active regulatory elements can interact over ultra-long distances, influenced by factor clustering and independent of transcription machinery.