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Chromatin accessibility and transcriptional landscape in PK-15 cells during early exposure to Aflatoxin B1

Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect...

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Published in:Biochemical and biophysical research communications 2024-10, Vol.731, p.150394, Article 150394
Main Authors: Li, Congcong, Liu, Xiangdong, Liu, Jiaxin, Zhang, Xuanxuan, Wu, Jiao, Ji, Xiangbo, Niu, Hui, Xu, Qiuliang
Format: Article
Language:English
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Summary:Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect of AFB1 remains unclear. In this study, we used assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to uncover chromatin accessibility and gene expression dynamics in PK-15 cells during early exposure to AFB1. We observed that the toxic effects of AFB1 involve signaling pathways such as p53, PI3K-AKT, Hippo, MAPK, TLRs, apoptosis, autophagy, and cancer pathways. Basic leucine zipper (bZIP) transcription factors (TFs), including AP-1, Fos, JunB, and Fra2, play a crucial role in regulating the biological processes involved in AFB1 challenge. Several new TFs, such as BORIS, HNF1b, Atf1, and KNRNPH2, represent potential targets for the toxic mechanism of AFB1. In addition, it is crucial to focus on the concentration of intracellular zinc ions. These findings will contribute to a better understanding of the mechanisms underlying AFB1-induced nephrotoxicity and offer new molecular targets. •The epigenetic and transcriptional regulation involved in PK-15 cell exposure to AFB1.•Basic leucine zipper transcription factors play crucial roles during exposure to AFB1.•De novo motifs represent potential new targets for AFB1 toxicity mechanisms.
ISSN:0006-291X
1090-2104
1090-2104
DOI:10.1016/j.bbrc.2024.150394