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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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Regulation of Expression Occurs at Multiple Steps02:24

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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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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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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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General Transcription Factors01:30

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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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T Cell Types and Functions01:24

T Cell Types and Functions

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Na&#239;ve CD4+ T Cells Using a TGF-&#946;-containing Protocol
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Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1.

Masahiro Ono1, Hiroko Yaguchi, Naganari Ohkura

  • 1Department of Experimental Pathology, Institute for Frontier Medical Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Nature
|March 23, 2007
PubMed
Summary

Regulatory T cells (T(R) cells) maintain immune balance. The transcription factor Foxp3 interacts with AML1 to suppress IL-2 and IFN-gamma, controlling T(R) cell function and immune responses.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Transcription Factor Function

Background:

  • Naturally arising CD25+CD4+ regulatory T cells (T(R) cells) are crucial for maintaining immunological self-tolerance and immune homeostasis.
  • T(R) cells suppress aberrant immune responses, preventing autoimmune diseases and allergies.
  • The transcription factor Foxp3 is a key regulator of T(R)-cell development and function, and its ectopic expression confers suppressive activity.

Purpose of the Study:

  • To elucidate the molecular mechanism by which Foxp3 controls T(R)-cell function, including cytokine production and the expression of T(R)-cell-associated molecules.
  • To investigate the role of the transcription factor AML1 (acute myeloid leukaemia 1)/Runx1 in regulating T(R)-cell-associated gene expression.
  • To explore the potential of targeting the Foxp3-AML1 interaction for controlling T-cell-mediated immune responses.

Main Methods:

  • Investigated the interaction between Foxp3 and AML1 in natural T(R) cells.
  • Analyzed the effect of this interaction on the gene expression of IL-2 and IFN-gamma.
  • Assessed the impact on the upregulation of T(R)-cell-associated molecules and overall suppressive activity.

Main Results:

  • Demonstrated that AML1/Runx1 activates IL-2 and IFN-gamma gene expression in conventional CD4+ T cells.
  • Showed that Foxp3 physically interacts with AML1 in natural T(R) cells.
  • Provided evidence that this Foxp3-AML1 interaction suppresses IL-2 and IFN-gamma production, upregulates T(R)-cell molecules, and confers suppressive activity.

Conclusions:

  • The interaction between Foxp3 and AML1 is a key mechanism controlling T(R)-cell function and suppressive activity.
  • This transcriptional control by Foxp3 and AML1 is essential for maintaining immune homeostasis.
  • Targeting the Foxp3-AML1 interaction offers a potential strategy for modulating T-cell-mediated immune responses in physiological and pathological conditions.