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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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Author Spotlight: Epigenetic Modifications and Metabolic Rewiring as Targets for Cancer Therapy
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Investigating pathological epigenetic aberrations by epi-proteomics.

Giulia Robusti1, Alessandro Vai1, Tiziana Bonaldi1,2

  • 1Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139, Milan, Italy.

Clinical Epigenetics
|November 12, 2022
PubMed
Summary

Epigenetics research uses mass spectrometry to analyze histone modifications and variants in clinical samples. This "epi-proteomics" approach offers advantages over traditional methods for biomarker discovery and therapeutic target identification in diseases like cancer.

Keywords:
CancerEpigeneticsHistone posttranslational modificationHistone variantHistone-modifying enzymeMass spectrometryProteomics

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Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Epigenetics regulates gene activity without altering DNA sequence, crucial for cell differentiation.
  • Aberrant epigenetic modifications, including histone posttranslational modifications (PTMs) and variants, are linked to diseases such as cancer.
  • Histone PTMs and variants serve as biomarkers for patient stratification and potential therapeutic targets.

Purpose of the Study:

  • To provide a critical overview of mass spectrometry (MS)-based approaches for studying histone PTMs and variants in clinical samples.
  • To highlight recent advances in epi-proteomics for investigating epigenetic mechanisms in disease.
  • To discuss challenges and future directions for MS-based epi-proteomics in clinical research.

Main Methods:

  • Mass spectrometry (MS) for comprehensive, unbiased, and quantitative analysis of histone proteoforms.
  • Review of MS-based techniques applied to clinical samples for profiling histone modifications and variants.
  • Discussion of advanced MS applications, including uncommon modifications and multi-omics integration.

Main Results:

  • MS-based epi-proteomics offers significant advantages over traditional antibody-based methods for analyzing clinical samples.
  • Epi-proteomics enables detailed investigation of histone PTMs and variants in pathological conditions.
  • Recent advances facilitate the analysis of rare modifications and integration with other omics data.

Conclusions:

  • MS-based epi-proteomics is a powerful tool for understanding epigenetic dysregulation in disease.
  • This approach holds promise for identifying novel biomarkers and therapeutic strategies.
  • Further development is needed to fully realize the potential of epi-proteomics in clinical applications.