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Epigenetic Regulation01:46

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Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Epigenetic Regulation01:37

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Immunodeficiency Diseases01:25

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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Epigenetic Priming in Immunodeficiencies.

Jorge Martínez-Cano1, Elena Campos-Sánchez1, César Cobaleda1

  • 1Department of Cell Biology and Immunology, Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Científicas -Universidad Autónoma de Madrid), Madrid, Spain.

Frontiers in Cell and Developmental Biology
|July 30, 2019
PubMed
Summary

Epigenetics, alongside genetics and environmental factors, is proposed as a crucial third axis in understanding immunodeficiencies (IDs). This framework links primary and secondary IDs, suggesting new therapeutic targets for these immune system disorders.

Keywords:
agingdevelopmental syndromesenvironmental exposuresepigeneticsinfectionsprimary immunodeficienciessecondary immunodeficiencies

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Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • Immunodeficiencies (IDs) increase susceptibility to infections and cancer, leading to high morbidity and mortality.
  • Primary IDs (PIDs) are genetic, often involving B-cell defects, while secondary IDs (SIDs) result from environmental exposures.
  • Epigenetic control is vital for B-cell differentiation and immune cell function.

Purpose of the Study:

  • To propose epigenetics as a "third axis" in the etiology of immunodeficiencies, alongside genetics and environmental agents.
  • To link primary and secondary immunodeficiencies at a molecular level by considering epigenetic contributions.
  • To highlight the potential of epigenetic modifications as therapeutic targets for IDs.

Main Methods:

  • Review and synthesis of current research on genetic and environmental factors in IDs.
  • Analysis of next-generation sequencing data implicating epigenetic regulators in PIDs.
  • Parallelism drawn between the role of epigenetics in cancer and its potential role in IDs.

Main Results:

  • Epigenetic alterations are increasingly identified in both primary and secondary immunodeficiencies.
  • A continuum model is proposed where IDs arise from combinations of genetic, environmental, and epigenetic factors.
  • The study suggests that some IDs may be triggered solely by epigenetic mechanisms.

Conclusions:

  • Epigenetics represents a critical, often reversible, factor in the development of immunodeficiencies.
  • This unified etiological framework blurs the distinction between primary and secondary IDs.
  • Understanding the epigenetic basis of IDs offers significant prophylactic and translational therapeutic opportunities.