1. Modulation of Chromatin Remodelling Induced by the Freshwater Cyanotoxin Cylindrospermopsin in Human Intestinal Caco-2 Cells
- Author
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Romain Villot, Aurélie Hatton, Hélène Quenault, Yannick Blanchard, Antoine Huguet, Valérie Fessard, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Laboratoire de Ploufragan - Plouzané
- Subjects
Methyltransferase ,Cellular differentiation ,lcsh:Medicine ,Toxicology ,chemistry.chemical_compound ,Histocompatibility Antigens ,cylindrospermopsin ,toxicité ,Toxins ,lcsh:Science ,Histone Acetyltransferases ,Lysine Acetyltransferase 5 ,Multidisciplinary ,Cyanobacteria Toxins ,biology ,cyanotoxin ,Genomics ,caco-2: freshwater ,3. Good health ,Cell biology ,Histone ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,Transcriptome Analysis ,Research Article ,Cyclin-Dependent Kinase Inhibitor p21 ,human intestinal caco-2 cell ,cyanotoxine ,DNA repair ,Ubiquitin-Protein Ligases ,Bacterial Toxins ,Toxic Agents ,Down-Regulation ,Histone H3 ,Alkaloids ,Genetics ,Humans ,Uracil ,KAT5 ,Toxicity ,lcsh:R ,toxicologie ,Biology and Life Sciences ,Computational Biology ,Histone-Lysine N-Methyltransferase ,Chromatin Assembly and Disassembly ,Genome Analysis ,Molecular biology ,Enterocytes ,chemistry ,cylindrospermopsine ,CCAAT-Enhancer-Binding Proteins ,biology.protein ,lcsh:Q ,Cylindrospermopsin ,Caco-2 Cells - Abstract
International audience; Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 mM for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes). Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2) involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5) and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN.
- Published
- 2014
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