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Related Concept Videos

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

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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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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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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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Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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The Eukaryotic Promoter Region02:40

The Eukaryotic Promoter Region

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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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Related Experiment Video

Updated: Mar 8, 2026

Author Spotlight: An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
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Systematic dissection of genomic features determining transcription factor binding and enhancer function.

Sharon R Grossman1,2,3, Xiaolan Zhang1, Li Wang1

  • 1Broad Institute, Cambridge, MA 02142.

Proceedings of the National Academy of Sciences of the United States of America
|February 1, 2017
PubMed
Summary

Understanding transcription factor (TF) binding and enhancer activity is key. This study reveals distinct features govern TF binding versus enhancer function, highlighting TF interactions for gene regulation.

Keywords:
gene regulationsystems biologytranscription factor binding

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Area of Science:

  • Genomics
  • Molecular Biology
  • Gene Regulation

Background:

  • Enhancers control gene expression via transcription factor (TF) binding to specific DNA motifs.
  • TF binding and enhancer function are influenced by chromatin state, binding site affinity, TF activity, and TF interactions.
  • The exact contributions of these factors to regulatory element function are not fully understood.

Purpose of the Study:

  • To systematically dissect the features governing TF binding and enhancer activity.
  • To investigate the role of PPARγ (a key adipogenesis regulator) binding and activity.
  • To characterize TF interactions and their impact on enhancer function.

Main Methods:

  • Utilized massively parallel reporter assays (MPRAs) with 32,115 enhancers (natural and synthetic).
  • Employed high-throughput in vivo binding assays.
  • Systematically analyzed features influencing PPARγ binding and enhancer activity.

Main Results:

  • Distinct feature sets regulate PPARγ binding versus enhancer activity.
  • PPARγ binding depends on motif affinity and locus features like chromatin accessibility.
  • Enhancer activity relies on numerous nearby TFs and their combinatorial interactions, with varied interaction rules (subadditive, additive, superadditive) and grammars.

Conclusions:

  • Provides a systematic framework for characterizing genomic features of regulatory elements.
  • Applicable to designing synthetic regulatory elements.
  • Offers insights for interpreting human genetic variation related to gene regulation.