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Related Concept Videos

Co-activators and Co-repressors02:04

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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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T Cell Types and Functions01:24

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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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Master Transcription Regulators02:23

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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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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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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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Related Experiment Video

Updated: Jun 9, 2025

Retroviral Transduction of Helper T Cells as a Genetic Approach to Study Mechanisms Controlling their Differentiation and Function
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Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function.

Valentina Stolz1, Rafael de Freitas E Silva1, Ramona Rica1

  • 1Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Vienna, Austria.

Elife
|October 28, 2024
PubMed
Summary

Nuclear receptor corepressor 1 (NCOR1) maintains immune balance by regulating T regulatory (Treg) cell states. NCOR1 deficiency impairs Treg cell function and transcriptional integrity, impacting immune homeostasis.

Keywords:
T lymphocyte subsetsautoimmunityhuman cd4+ t cellsimmunologyinflammationmouseregulatory T cells

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Area of Science:

  • Immunology
  • Epigenetics
  • Cell Biology

Background:

  • FOXP3+ regulatory T cells (Treg cells) are crucial for maintaining immune homeostasis.
  • The molecular mechanisms governing Treg cell differentiation and function are complex and incompletely understood.
  • Epigenetic regulators play a significant role in controlling immune cell states.

Purpose of the Study:

  • To investigate the role of nuclear receptor corepressor 1 (NCOR1) in regulating Treg cell states.
  • To determine the impact of NCOR1 deficiency on Treg cell function and transcriptional integrity.
  • To explore the relationship between NCOR1, cholesterol homeostasis, and Treg cell subset composition.

Main Methods:

  • Utilized NCOR1 deletion models in mice.
  • Generated in vitro human Treg cells.
  • Performed gene expression analysis to assess transcriptional integrity and effector/naïve gene signatures.
  • Investigated the role of liver X receptor (LXR) signaling.

Main Results:

  • NCOR1 deletion led to increased effector Treg cell frequencies in mice and human cells.
  • NCOR1-deficient Treg cells exhibited impaired suppressive function in a mouse model of colitis.
  • NCOR1 deficiency disrupted the transcriptional integrity of Treg cells, with effector signatures upregulated in naïve cells and naïve signatures repressed in effector cells.
  • Genes related to cholesterol homeostasis and LXR targets were dysregulated in NCOR1-deficient Treg cells.
  • NCOR1's control over Treg cell subset composition was independent of LXRβ signaling.

Conclusions:

  • NCOR1 is essential for maintaining the transcriptional integrity of both naïve and effector Treg cell states.
  • NCOR1 plays a critical role in supporting the in vivo suppressive functions of Treg cells.
  • NCOR1 acts as an important epigenetic regulator in Treg cell biology, independent of LXRβ pathways.