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Related Concept Videos

RNA Polymerase II Accessory Proteins02:36

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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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Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
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RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
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The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences.  The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
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RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
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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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RNA polymerase II dynamics shape enhancer-promoter interactions.

Gilad Barshad1, James J Lewis1,2, Alexandra G Chivu1

  • 1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.

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Summary

Enhancers communicate with target genes over long genomic distances. Transcriptional dynamics, particularly RNA polymerase II (Pol II) pausing, stabilize these crucial enhancer-promoter interactions.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Gene Regulation

Background:

  • Enhancer-promoter communication is vital for gene expression.
  • Mechanisms controlling long-range interactions remain unclear.

Purpose of the Study:

  • Investigate how enhancers communicate with target genes over long genomic distances.
  • Elucidate the role of transcriptional dynamics in enhancer-promoter interactions.

Main Methods:

  • Integrated nucleosome-resolution genomic contact maps (Micro-C) with nascent transcription data.
  • Utilized CRISPR interference (CRISPRi) to perturb RNA polymerase II (Pol II) dynamics and enhancer activity.
  • Analyzed functional vs. nonfunctional enhancer-promoter pairs.

Main Results:

  • Functional enhancer-promoter pairs exhibit longer proximity durations.
  • Proximity is influenced by factors beyond genomic position.
  • RNA polymerase II (Pol II) plays a critical role in stabilizing interactions.
  • Promoter-proximal paused Pol II partially stabilizes enhancer-promoter contacts.

Conclusions:

  • Transcriptional dynamics, including Pol II pausing, are key regulators of enhancer-promoter interaction frequency and duration.
  • An updated model proposes transcriptional dynamics shape interactions to facilitate gene regulation over long distances.