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University of Dundee Xenobiotic CAR University of Dundee Xenobiotic CAR activators induce Dlk1-Dio3 locus non-coding RNA expression in mouse liver Pouché , Lucie; Vitobello, Antonio; Römer, Michael ; Glogovac, Milica ; MacLeod, A. Kenneth; Ellinger-Ziegelbauer, Heidrun Published in: Toxicological Sciences DOI: 10.1093/toxsci/kfx104 Publication date: 2017 Document Version Peer reviewed version Link to publication in Discovery Research Portal Citation for published version (APA): Pouché , L., Vitobello, A., Römer, M., Glogovac, M., MacLeod, A. K., Ellinger-Ziegelbauer, H., Westphal, M., Dubost, V., Stiehl, D. P., Dumotier, B., Fekete, A., Moulin, P., Zell, A., Schwarz, M., Moreno , R., Huang, J. T. J., Elcombe, C. R., Henderson, C. J., Wolf, C. R., ... Terranova, R. (2017). Xenobiotic CAR activators induce Dlk1- Dio3 locus non-coding RNA expression in mouse liver. Toxicological Sciences, 158(2), 367-378. https://doi.org/10.1093/toxsci/kfx104 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 06. Oct. 2021 Toxicological Sciences Xenobiotic CAR activators induce Dlk1-Dio3 locus non- coding RNA expression in mouse liver Journal: Toxicological Sciences Manuscript ID TOXSCI-16-0705.R1 Manuscript Type: Research Article Date Submitted by the Author: n/a Complete List of Authors: Pouche, Lucie; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Vitobello, Antonio; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Römer, Michael; University of Tübingen, Department of Computer Science Glogovac, Milica; Novartis Pharma AG, Novartis Business Services MacLeod, A. Kenneth; University of Dundee, Division of Cancer Research, Jacqui Wood Cancer Centre Ellinger-Ziegelbauer, Heidrun; Bayer Pharma AG, Westphal, Magdalena; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Dubost, Valerie; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Stiehl, Daniel; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Dumotier, Bérengère; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Fekete, Alexander; Novartis Institutes for Biomedical Research Moulin, Pierre; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Zell, Andreas; University of Tübingen, Center for Bioinformatics Schwarz, Michael; University of Tuebingen, Toxicology; Moreno, Rita; University of Dundee, Division of Cancer Research, Jacqui Wood Cancer Centre Huang, Jeffrey T. J. ; University of Dundee, Biomarker and Drug Analysis Core Facility, School of Medicine Elcombe, Clifford; CXR Biosciences, ; Henderson, Colin; University of Dundee, Cancer Research UK, Molecular Pharmacology Unit Wolf, C. Roland; University of Dundee, Cancer Research UK, Medical Research Institute Moggs, Jonathan; Novartis Pharma AG, Safety Profiling & Assessment, Investigative Toxicology Terranova, Remi; Novartis Institutes for Biomedical Research, Preclinical Safety, Translational Medicine Cancer Risk Assessment, Constitutive Androstane Receptor (CAR), Key Words: biomarkers < Safety Evaluation, non-genotoxic < Carcinogenesis, Dlk1- This is a pre-copyedited, author-produced version of an article accepted for publication in Toxicological Sciences following peer review. The version of record 'Xenobiotic CAR activators induce Dlk1-Dio3 locus non-coding RNA experssion in mouse live', Toxciological Sciences, is available online at: https://doi.org/10.1093/toxsci/kfx104. Page 1 of 45 Toxicological Sciences 1 2 3 4 Dio3 cluster long non-coding RNAs 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Toxicological Sciences Page 2 of 45 1 2 3 4 Xenobiotic CAR activators induce Dlk1- 5 6 7 Dio3 locus non-coding RNA expression in 8 9 mouse liver 10 11 12 13 14 Lucie Pouché*, Antonio Vitobello*, Michael Römer 1, Milica Glogovac, A. Kenneth 15 16 MacLeod, Heidrun Ellinger-Ziegelbauer 1, Magdalena Westphal, Valérie Dubost, 17 18 19 Daniel Philipp Stiehl, Bérengère Dumotier, Alexander Fekete, Pierre Moulin, Andreas 20 1 1 1 21 Zell , Michael Schwarz , Rita Moreno, Jeffrey T. J. Huang, Cliff R. Elcombe , Colin J. 22 23 Henderson 1, C. Roland Wolf 1, Jonathan G. Moggs 1, Rémi Terranova** 24 25 26 27 Author affiliations: 28 29 30 Lucie Pouché: * contributed equally to this work , Preclinical Safety, Translational 31 32 Medicine, Novartis Institutes for Biomedical Research, CH-4057 Basel, Switzerland, 33 34 [email protected] 35 36 37 Antonio Vitobello: * contributed equally to this work , Preclinical Safety, Translational 38 39 40 Medicine, Novartis Institutes for Biomedical Research, CH-4057 Basel, Switzerland, 41 42 [email protected] 43 44 45 Milica Glogovac: Novartis Business Services, Novartis Pharma, CH-4057 Basel, 46 47 Switzerland, [email protected] 48 49 50 Michael Römer: Department of Computer Science, University of Tübingen, Sand 1, 51 52 72076 Tübingen, Germany, [email protected] 53 54 55 56 57 58 59 60 1 Page 3 of 45 Toxicological Sciences 1 2 3 A. Kenneth MacLeod: Division of Cancer Research, Jacqui Wood Cancer Centre, 4 5 University of Dundee, James Arrott Drive, Ninewells Hospital And Medical School, 6 7 Dundee, DD1 9SY, United Kingdom, [email protected] 8 9 10 Heidrun Ellinger-Ziegelbauer: Investigational Toxicology, GDD-GED-Toxicology, 11 12 13 Bayer Pharma AG, 42096 Wuppertal, Germany, heidrun.ellinger- 14 15 [email protected] 16 17 18 Magdalena Westphal: Preclinical Safety, Translational Medicine, Novartis Institutes 19 20 for Biomedical Research, CH-4057 Basel, Switzerland, 21 22 [email protected] 23 24 25 Valérie Dubost: Preclinical Safety, Translational Medicine, Novartis Institutes for 26 27 28 Biomedical Research, CH-4057 Basel, Switzerland, 29 30 [email protected] 31 32 33 Daniel Philipp Stiehl: Preclinical Safety, Translational Medicine, Novartis Institutes for 34 35 Biomedical Research, CH-4057 Basel, Switzerland, [email protected] 36 37 38 Bérengère Dumotier: Preclinical Safety, Translational Medicine, Novartis Institutes for 39 40 Biomedical Research, CH-4057 Basel, Switzerland, 41 42 43 [email protected] 44 45 46 Alexander Fekete: Preclinical Safety, Translational Medicine, Novartis Institutes for 47 48 Biomedical Research, Inc. 250 Massachusetts Avenue, Cambridge, MA 02139, 49 50 United States, [email protected] 51 52 53 Pierre Moulin: Preclinical Safety, Translational Medicine, Novartis Institutes for 54 55 Biomedical Research, CH-4057 Basel, Switzerland, [email protected] 56 57 58 59 60 2 Toxicological Sciences Page 4 of 45 1 2 3 Andreas Zell: Department of Computer Science, University of Tübingen, Sand 1, 4 5 72076 Tübingen, Germany, [email protected] 6 7 8 Michael Schwarz: Department of Toxicology, University of Tübingen, Wilhelmstr. 56, 9 10 72074 Tübingen, Germany, [email protected] 11 12 13 Rita Moreno: Division of Cancer Research, Jacqui Wood Cancer Centre, University 14 15 16 of Dundee, James Arrott Drive, Ninewells Hospital And Medical School, Dundee, 17 18 DD1 9SY, United Kingdom, [email protected] 19 20 21 Jeffrey T. J. Huang: Biomarker and Drug Analysis Core Facility, School of Medicine, 22 23 University of Dundee, Jacqui Wood Cancer Centre, Ninewells Hospital, Dundee, DD1 24 25 9SY, United Kingdom, [email protected] 26 27 28 Cliff R. Elcombe: CXR Biosciences Ltd., 2 James Lindsay Place, Dundee 29 30 31 Technopole, Dundee Scotland DD1 5JJ, [email protected] 32 33 34 Colin J. Henderson: Division of Cancer Research, Jacqui Wood Cancer Centre, 35 36 University of Dundee, James Arrott Drive, Ninewells Hospital And Medical School, 37 38 Dundee, DD1 9SYMedical Research Institute, University of Dundee, Dundee, United 39 40 41 Kingdom, [email protected] 42 43 44 C. Roland Wolf: Division of Cancer Research, Jacqui Wood Cancer Centre, 45 46 University of Dundee, James Arrott Drive, Ninewells Hospital And Medical School, 47 48 49 Dundee, DD1 9SYMedical Research Institute, University of Dundee, Dundee, United 50 51 Kingdom, [email protected] 52 53 54 Jonathan G. Moggs: Preclinical Safety, Translational Medicine, Novartis Institutes for 55 56 Biomedical Research, CH-4057 Basel, Switzerland, [email protected] 57 58 59 60 3 Page 5 of 45 Toxicological Sciences 1 2 3 Rémi Terranova: **corresponding author, Preclinical Safety, Translational Medicine, 4 5 Novartis Institutes for Biomedical Research, CH-4057 Basel, Switzerland, 6 7 [email protected] 8 9 10 11 12 13 1MARCAR consortium member 14 15 16 *Contributed
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