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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

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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...
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Transcription Factors02:16

Transcription Factors

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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...
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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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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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Cis-regulatory Sequences02:02

Cis-regulatory Sequences

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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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Co-activators and Co-repressors02:04

Co-activators and Co-repressors

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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 Regulators02:23

Master Transcription Regulators

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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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Position-dependent function of human sequence-specific transcription factors.

Sascha H Duttke1, Carlos Guzman2, Max Chang2

  • 1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA. sascha.duttke@wsu.edu.

Nature
|July 17, 2024
PubMed
Summary
This summary is machine-generated.

Transcription factor (TF) binding site position relative to the transcription start site (TSS) dictates gene regulation. This positional dependence explains how similar TF binding sites generate diverse gene expression patterns and contribute to disease.

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Area of Science:

  • Genomics and Molecular Biology
  • Gene Regulation and Transcription

Background:

  • Regulatory elements like promoters and enhancers contain transcription factor (TF) binding sites.
  • Understanding how these sites encode gene expression is crucial for gene regulation and disease research.
  • Similar TF binding site arrangements can lead to different gene expression outcomes.

Purpose of the Study:

  • To investigate the role of TF binding site position relative to the transcription start site (TSS) in gene regulation.
  • To determine how spatial configuration of TF binding sites influences transcription initiation.
  • To elucidate mechanisms by which DNA sequence variations contribute to transcriptional variation and disease.

Main Methods:

  • Analysis of gene regulation from the perspective of individual TSSs.
  • Utilized natural genetic variation, perturbation of endogenous TF protein levels, and massively parallel reporter assays.
  • Analyzed TF binding site occurrences relative to the TSS to identify positional preferences.

Main Results:

  • Demonstrated that the effect of TF binding on transcription initiation is position-dependent.
  • Identified several TF binding motifs with highly preferential positioning relative to the TSS.
  • Showed that TFs can activate or repress transcription initiation based on their precise position relative to the TSS.

Conclusions:

  • TF binding site position and spacing collectively guide the site and frequency of transcription initiation.
  • Revealed how similar TF binding site assortments generate distinct gene regulatory outcomes based on spatial configuration.
  • Highlighted the critical role of TSS data in decoding genomic regulatory information and understanding disease mechanisms.