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Related Concept Videos

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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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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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Lymphoid cells and tissues are integral to the immune system, which is crucial in maintaining our body's defense against harmful pathogens. They form the building blocks of lymphoid organs, which include the spleen, thymus, and lymph nodes.
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FOXO1 and FOXO3 Cooperatively Regulate Innate Lymphoid Cell Development.

Thuy T Luu1,2, Jonas Nørskov Søndergaard3, Lucía Peña-Pérez2,4

  • 1Department of Medicine Huddinge, Huddinge, Karolinska Institute, Stockholm, Sweden.

Frontiers in Immunology
|June 27, 2022
PubMed
Summary
This summary is machine-generated.

FOXO1 and FOXO3 transcription factors are crucial for natural killer (NK) cell development and function. Their coordinated action regulates key genes, ensuring proper NK cell maturation and survival.

Keywords:
FOXOIL-15developmentinnate lymphocyte cells (ILCs)natural killer cells

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Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • Natural killer (NK) cells are vital for immunity against viruses and cancer.
  • Mechanisms governing NK cell development and function require further elucidation.

Purpose of the Study:

  • To identify cell fate-determining pathways in NK cell progenitors (NKP).
  • To investigate the roles of FOXO1 and FOXO3 in NK cell development and lineage commitment.

Main Methods:

  • Comprehensive gene expression profiling of NK cell progenitors.
  • Transcriptome and chromatin profiling.
  • Analysis of FOXO1 and FOXO3 deficient murine models.

Main Results:

  • FOXO1 and FOXO3 are co-expressed throughout NK cell development.
  • Loss of FOXO1 and FOXO3 impairs NK cell program establishment, development, and maturation.
  • Combined FOXO1/FOXO3 deficiency alters innate lymphoid cell (ILC) subset composition.
  • FOXO TFs orchestrate distinct molecular mechanisms for NK cell development.
  • Deficiency reduces expression of NK cell development genes like ETS-1.
  • FOXO1 and FOXO3 regulate IL-15Rβ (CD122) for NK cell survival.

Conclusions:

  • FOXO1 and FOXO3 act coordinately to regulate essential developmental genes at multiple stages of murine NK cell and ILC lineage commitment.
  • These transcription factors are critical for establishing the NK cell program and ensuring proper maturation and survival.