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Related Experiment Video

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Aflatoxin B1 induced multiple epigenetic modulators in human epithelial cell lines.

Priyanka Soni1, Md Sajid Ghufran1, Santosh R Kanade1

  • 1Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Kasargod 671314, Kerala, India.

Toxicon : Official Journal of the International Society on Toxinology
|July 15, 2018
PubMed
Summary

Aflatoxin B1, a toxic compound from Aspergillus flavus, alters host cell function by modulating epigenetic regulators. This study reveals its impact on DNA methyltransferases, histone modifiers, and polycomb proteins, potentially driving oncogenesis.

Keywords:
Aflatoxin B(1)DNMTsHATHDACsPolycomb repressor complex

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Area of Science:

  • Toxicology
  • Epigenetics
  • Molecular Biology

Background:

  • Aflatoxin B1 (AFB1) is a potent toxicant produced by Aspergillus flavus, posing significant health risks.
  • AFB1 exerts its harmful effects through various genetic and non-genetic pathways, with epigenetic mechanisms gaining attention.
  • Understanding AFB1's impact on epigenetic regulators is crucial for elucidating its role in disease, particularly cancer.

Purpose of the Study:

  • To investigate the functional expression profile of multiple epigenetic regulators affected by AFB1.
  • To determine how AFB1 modulates DNA methyltransferases (DNMTs), histone-modifying enzymes, and polycomb proteins.
  • To elucidate the epigenetic alterations induced by AFB1 that are relevant to oncogenic processes.

Main Methods:

  • Analysis of gene and protein expression levels of DNMTs, histone acetyltransferases (HATs), histone deacetylases (HDACs), BMI-1, and EZH2.
  • Assay of HAT and HDAC activities.
  • Assessment of H3K27 trimethylation and H2AK119 ubiquitination.

Main Results:

  • AFB1 upregulated DNMTs at both gene and protein levels in a dose-dependent manner.
  • AFB1 significantly reduced HAT activity while increasing HDAC activity, alongside elevated HDAC gene and protein expression.
  • AFB1 significantly overexpressed BMI-1 and EZH2, leading to increased H3K27 trimethylation and H2AK119 ubiquitination.

Conclusions:

  • AFB1 significantly impacts multiple epigenetic modulators, including DNMTs, HATs, HDACs, BMI-1, and EZH2.
  • These AFB1-induced epigenetic changes, such as altered histone modifications and polycomb protein expression, are implicated in oncogenic pathways.
  • The findings highlight the critical role of epigenetic dysregulation in aflatoxin-induced toxicity and cancer development.