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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

Insights

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.

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.
Keywords:
Aflatoxin B(1)DNMTsHATHDACsPolycomb repressor complex

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