title: Modulation of chromatin remodelling induced by the freshwater cyanotoxin cylindrospermopsin in human intestinal caco-2 cells.
abstract: 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 µM 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.
authors.affiliation: Contaminant Toxicology Unit, Fougères Laboratory, Anses, Fougères Cedex, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Huguet
authors.affiliation: Contaminant Toxicology Unit, Fougères Laboratory, Anses, Fougères Cedex, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hatton
authors.affiliation: Contaminant Toxicology Unit, Fougères Laboratory, Anses, Fougères Cedex, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Villot
authors.affiliation: Viral Genetics and Bio-security Unit, Ploufragan-Plouzané Laboratory, Anses, Site des Croix, Ploufragan, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Quenault
authors.affiliation: Viral Genetics and Bio-security Unit, Ploufragan-Plouzané Laboratory, Anses, Site des Croix, Ploufragan, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Blanchard
authors.affiliation: Contaminant Toxicology Unit, Fougères Laboratory, Anses, Fougères Cedex, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Fessard
mesh_terms: D000470:Alkaloids; D001427:Bacterial Toxins; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D042002:Chromatin Assembly and Disassembly; D000087522:Cyanobacteria Toxins; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D044767:Ubiquitin-Protein Ligases; D014498:Uracil / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000470:Alkaloids; D001427:Bacterial Toxins; D022762:CCAAT-Enhancer-Binding Proteins; C493956:CDKN1A protein, human; D000087522:Cyanobacteria Toxins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006649:Histocompatibility Antigens; C089595:cylindrospermopsin; D014498:Uracil; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; C496552:KAT8 protein, human; D000074443:Lysine Acetyltransferase 5; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases