title: Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress.
abstract: The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here we show a global decrease of hydroxymethylcytosine in cells treated with buthionine sulfoximine, and in mice depleted for the major antioxidant enzymes GPx1 and 2. Furthermore, genome-wide profiling revealed differentially hydroxymethylated regions in coding genes, and intriguingly in microRNA genes, both involved in response to oxidative stress. These results thus suggest a profound effect of in vivo oxidative stress on the global hydroxymethylome.
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Delatte
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Jana
authors.initials: J
authors.lastname: Jeschke
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Defrance
authors.affiliation: CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Bachman
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Creppe
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Emilie
authors.initials: E
authors.lastname: Calonne
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Bizet
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Rachel
authors.initials: R
authors.lastname: Deplus
authors.affiliation: ULB, Center for Diabetes Research, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Laura
authors.initials: L
authors.lastname: Marroquí
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Libin
authors.affiliation: Institute of Biochemistry, Stuttgart University, 70569 Stuttgart, Germany.
authors.forename: Mirunalini
authors.initials: M
authors.lastname: Ravichandran
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Françoise
authors.initials: F
authors.lastname: Mascart
authors.affiliation: ULB, Center for Diabetes Research, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: Decio L
authors.initials: DL
authors.lastname: Eizirik
authors.affiliation: CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, United Kingdom.
authors.forename: Adele
authors.initials: A
authors.lastname: Murrell
authors.affiliation: Institute of Biochemistry, Stuttgart University, 70569 Stuttgart, Germany.
authors.forename: Tomasz P
authors.initials: TP
authors.lastname: Jurkowski
authors.affiliation: Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB, 1070 Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Fuks
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D049308:Dioxygenases; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D055106:Genome-Wide Association Study; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000963:Antimetabolites; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C540839:TET1 protein, mouse; D019328:Buthionine Sulfoximine; D044503:5-Methylcytosine; C492172:Gpx2 protein, mouse; D005979:Glutathione Peroxidase; D049308:Dioxygenases; C551914:Tet2 protein, mouse; D005978:Glutathione; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse