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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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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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Keepin' it regulatory: Foxp3 gets a BAFfling SWItch.

Maxime J Kinet1, Michael D Rosenblum2

  • 1Department of Dermatology, University of California, San Francisco, CA 94143, USA.

Science Immunology
|September 5, 2020
PubMed
Summary
This summary is machine-generated.

SWI/SNF complexes regulate the expression and activity of Foxp3, a key protein in regulatory T cells (Tregs). This discovery reveals a new mechanism controlling Treg function, crucial for immune system balance.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • Regulatory T cells (Tregs) are crucial for maintaining immune homeostasis and preventing autoimmunity.
  • The transcription factor Foxp3 is essential for Treg development and function.
  • Epigenetic regulators, such as SWI/SNF complexes, are increasingly recognized for their roles in immune cell differentiation.

Purpose of the Study:

  • To investigate the role of SWI/SNF complexes in regulating Foxp3 expression and activity in Tregs.
  • To elucidate the molecular mechanisms by which SWI/SNF complexes influence Treg function.

Main Methods:

  • CRISPR-Cas9 screening to identify epigenetic regulators of Foxp3.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) to map SWI/SNF binding sites.
  • Flow cytometry and gene expression analysis to assess Treg function and Foxp3 levels.
  • In vivo studies using mouse models of immune response.

Main Results:

  • SWI/SNF complexes were identified as novel regulators of Foxp3 expression in Tregs.
  • Depletion of SWI/SNF components led to altered Foxp3 levels and impaired Treg suppressive function.
  • SWI/SNF complexes directly bind to regulatory regions of the Foxp3 gene, influencing its epigenetic landscape.
  • Modulation of SWI/SNF activity impacted Treg-mediated suppression in vivo.

Conclusions:

  • SWI/SNF complexes play a critical, previously unrecognized role in fine-tuning Foxp3 expression and Treg activity.
  • Targeting SWI/SNF complexes may offer a therapeutic strategy for modulating Treg function in immune-related diseases.