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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

6.7K
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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Master Transcription Regulators

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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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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.
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Updated: Jan 11, 2026

In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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FOXP3 expression depends on cell-type-specific cis-regulatory elements and transcription factor circuitry.

Jennifer M Umhoefer1, Maya M Arce1, Sivakanthan Kasinathan2

  • 1Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA.

Immunity
|November 14, 2025
PubMed
Summary

Researchers identified regulatory elements controlling FOXP3 gene expression in T cells. This reveals how FOXP3 is specifically regulated in regulatory T cells (Treg cells) versus conventional T cells (Tconv cells) across species.

Keywords:
CRISPRFOXP3T cellsenhancersepigeneticsgene regulationregulatory T cellstranscription factors

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • FOXP3 is a crucial transcription factor (TF) defining regulatory T cells (Treg cells), essential for immune suppression.
  • Unlike in mice, human conventional CD4+ T cells (Tconv cells) can transiently express FOXP3 upon stimulation, indicating complex regulatory mechanisms.
  • Understanding the distinct regulation of FOXP3 expression between Treg and Tconv cells is vital for immunology research.

Purpose of the Study:

  • To identify cis-regulatory elements (CREs) controlling FOXP3 expression in human Treg and Tconv cells.
  • To discover trans-acting factors (TFs) that regulate FOXP3 expression.
  • To elucidate the cell- and species-specific mechanisms governing FOXP3 transcription.

Main Methods:

  • CRISPR screens were employed to tile the FOXP3 locus and target TFs in human Treg and Tconv cells.
  • Combinatorial silencing of identified CREs was performed to understand their epistatic relationships.
  • Mutagenesis of a murine negative regulatory element (NS- CRE) was conducted to assess its function.

Main Results:

  • A subset of Treg cell CREs, along with Tconv-cell-specific positive (NS+) and negative (NS-) CREs, were found to regulate FOXP3 expression in Tconv cells.
  • TF circuitry was mapped, identifying key regulators that occupy and control these CREs.
  • A murine NS- CRE was essential for restricting FOXP3 expression exclusively to Treg cells.

Conclusions:

  • Distinct cis-regulatory elements and trans-acting factors govern FOXP3 expression in a cell- and species-specific manner.
  • The study reveals the intricate circuitry controlling FOXP3 transcription, differentiating its expression patterns in Treg and Tconv cells.
  • Findings provide a foundation for understanding immune regulation and potential therapeutic targets.