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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Transcription Factors02:16

Transcription Factors

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...
Master Transcription Regulators02:23

Master Transcription Regulators

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...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...

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Related Experiment Video

Updated: May 8, 2026

Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
11:34

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Published on: August 9, 2019

STAT3 or USF2 contributes to HIF target gene specificity.

Matthew R Pawlus1, Liyi Wang, Aya Murakami

  • 1Molecular Biology Graduate Program, School of Dental Medicine University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Plos One
|August 31, 2013
PubMed
Summary

Hypoxia-inducible factors (HIF1 and HIF2) activate distinct genes in solid tumors. Specific transcription partners, STAT3 for HIF1 and USF2 for HIF2, dictate this gene activation specificity.

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • Hypoxia-inducible factors (HIF1 and HIF2) are crucial for solid tumor progression.
  • HIF1 and HIF2 activate unique gene subsets despite similar promoter binding.
  • The mechanism of HIF target gene specificity remains largely unknown.

Purpose of the Study:

  • To elucidate the mechanism of HIF target gene specificity.
  • To investigate the roles of STAT3 and USF2 in HIF-mediated transcription.
  • To determine how HIF1α and HIF2α interact with transcription partners.

Main Methods:

  • Reporter gene assays
  • Chromatin immunoprecipitation (ChIP)
  • siRNA and inhibitor studies
  • Analysis of protein-protein interactions and domain requirements

Main Results:

  • STAT3 and USF2 exhibit specific binding to HIF1 and HIF2 target gene promoters, respectively.
  • HIF1α interacts with STAT3, and HIF2α interacts with USF2, to activate their respective target genes.
  • Specific domains of HIF1α (HLH/PAS) and HIF2α (N- and C-TADs) mediate these interactions.
  • RNA Polymerase II recruitment is dependent on HIFs and their specific partners.

Conclusions:

  • HIF target gene specificity is achieved through distinct transcription partners (STAT3 for HIF1, USF2 for HIF2).
  • These partners bind specifically to target promoters and interact selectively with HIF1α or HIF2α.
  • This provides the first mechanistic insight into differential HIF target gene activation.