The role of chromatin-modifying enzymes and histone modifications in the modulation of p16 gene in fumonisin B1-induced toxicity in human kidney cells


Karaman E. F., Abudayyak M. F., Özden S.

Mycotoxin Research, vol.39, no.3, pp.271-283, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 3
  • Publication Date: 2023
  • Doi Number: 10.1007/s12550-023-00494-2
  • Journal Name: Mycotoxin Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.271-283
  • Keywords: Chromatin modifications, DNA methylation, Epigenetics, Fumonisin B1, Histone modifications, p16 gene
  • Istanbul University Affiliated: Yes

Abstract

Fumonisin B1 (FB1) poses a risk to animal and human health. Although the effects of FB1 on sphingolipid metabolism are well documented, there are limited studies covering the epigenetic modifications and early molecular alterations associated with carcinogenesis pathways caused by FB1 nephrotoxicity. The present study investigates the effects of FB1 on global DNA methylation, chromatin-modifying enzymes, and histone modification levels of the p16 gene in human kidney cells (HK-2) after 24 h exposure. An increase (2.23-fold) in the levels of 5-methylcytosine (5-mC) at 100 µmol/L was observed, a change independent from the decrease in gene expression levels of DNA methyltransferase 1 (DNMT1) at 50 and 100 µmol/L; however, DNMT3a and DNMT3b were significantly upregulated at 100 µmol/L of FB1. Dose-dependent downregulation of chromatin-modifying genes was observed after FB1 exposure. In addition, chromatin immunoprecipitation results showed that 10 µmol/L of FB1 induced a significant decrease in H3K9ac, H3K9me3 and H3K27me3 modifications of p16, while 100 µmol/L of FB1 caused a significant increase in H3K27me3 levels of p16. Taken together, the results suggest that epigenetic mechanisms might play a role in FB1 carcinogenesis through DNA methylation, and histone and chromatin modifications.