Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription

Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and... Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control of transcription, and understanding of the chemical effects on both could inform the causal role of epigenetic alterations in disease mechanisms. In this study, we hypothesized that baseline variability in chromatin organization and transcription profiles among various tissues and mouse strains influence the outcome of exposure to the DNA damaging chemical 1,3-butadiene. To test this hypothesis, we evaluated DNA damage along with comprehensive quantification of RNA transcripts (RNA-seq), identification of accessible chromatin (ATAC-seq), and characterization of regions with histone modifications associated with active transcription (ChIP-seq for acetylation at histone 3 lysine 27, H3K27ac). We collected these data in the lung, liver, and kidney of mice from two genetically divergent strains, C57BL/6J and CAST/EiJ, that were exposed to clean air or to 1,3-butadiene (~600 ppm) for 2 weeks. We found that tissue effects dominate differences in both gene expression and chromatin states, followed by strain effects. At baseline, xenobiotic metabolism was consistently more active in CAST/EiJ, while immune system pathways were more active in C57BL/6J across tissues. Surprisingly, even though all three tissues in both strains harbored butadiene-induced DNA damage, little transcriptional effect of butadiene was observed in liver and kidney. Toxicologically relevant effects of butadiene in the lung were on the pathways of xenobiotic metabolism and inflammation. We also found that variability in chromatin accessibility across individuals (i.e., strains) only partially explains the variability in transcription. This study showed that variation in the basal states of epigenome and transcriptome may be useful indicators for individuals or tissues susceptible to genotoxic environmental chemicals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Mammalian Genome Springer Journals

Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription

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Publisher
Springer US
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Life Sciences; Cell Biology; Animal Genetics and Genomics; Human Genetics
ISSN
0938-8990
eISSN
1432-1777
D.O.I.
10.1007/s00335-018-9739-6
Publisher site
See Article on Publisher Site

Abstract

Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control of transcription, and understanding of the chemical effects on both could inform the causal role of epigenetic alterations in disease mechanisms. In this study, we hypothesized that baseline variability in chromatin organization and transcription profiles among various tissues and mouse strains influence the outcome of exposure to the DNA damaging chemical 1,3-butadiene. To test this hypothesis, we evaluated DNA damage along with comprehensive quantification of RNA transcripts (RNA-seq), identification of accessible chromatin (ATAC-seq), and characterization of regions with histone modifications associated with active transcription (ChIP-seq for acetylation at histone 3 lysine 27, H3K27ac). We collected these data in the lung, liver, and kidney of mice from two genetically divergent strains, C57BL/6J and CAST/EiJ, that were exposed to clean air or to 1,3-butadiene (~600 ppm) for 2 weeks. We found that tissue effects dominate differences in both gene expression and chromatin states, followed by strain effects. At baseline, xenobiotic metabolism was consistently more active in CAST/EiJ, while immune system pathways were more active in C57BL/6J across tissues. Surprisingly, even though all three tissues in both strains harbored butadiene-induced DNA damage, little transcriptional effect of butadiene was observed in liver and kidney. Toxicologically relevant effects of butadiene in the lung were on the pathways of xenobiotic metabolism and inflammation. We also found that variability in chromatin accessibility across individuals (i.e., strains) only partially explains the variability in transcription. This study showed that variation in the basal states of epigenome and transcriptome may be useful indicators for individuals or tissues susceptible to genotoxic environmental chemicals.

Journal

Mammalian Genome – Springer Journals

Published: Feb 10, 2018

References

  • F-Seq: a feature density estimator for high-throughput sequence tags
    Boyle, AP; Guinney, J; Crawford, GE; Furey, TS
  • Interstrain differences in the liver effects of trichloroethylene in a multistrain panel of inbred mice
    Bradford, BU; Lock, EF; Kosyk, O; Kim, S; Uehara, T; Harbourt, D; DeSimone, M; Threadgill, DW; Tryndyak, V; Pogribny, IP; Bleyle, L; Koop, DR; Rusyn, I
  • Epigenetic events determine tissue-specific toxicity of inhalational exposure to the genotoxic chemical 1,3-butadiene in male C57BL/6J mice
    Chappell, G; Kobets, T; O’Brien, B; Tretyakova, N; Sangaraju, D; Kosyk, O; Sexton, KG; Bodnar, W; Pogribny, IP; Rusyn, I
  • Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: a systematic literature review
    Chappell, G; Pogribny, IP; Guyton, KZ; Rusyn, I
  • Variation in DNA-damage responses to an inhalational carcinogen (1,3-butadiene) in relation to strain-specific differences in chromatin accessibility and gene transcription profiles in C57BL/6J and CAST/EiJ mice
    Chappell, GA; Israel, JW; Simon, JM; Pott, S; Safi, A; Eklund, K; Sexton, KG; Bodnar, W; Lieb, JD; Crawford, GE; Rusyn, I; Furey, TS
  • Principles of regulatory information conservation between mouse and human
    Cheng, Y; Ma, Z; Kim, BH; Wu, W; Cayting, P; Boyle, AP; Sundaram, V; Xing, X; Dogan, N; Li, J; Euskirchen, G; Lin, S; Lin, Y; Visel, A; Kawli, T; Yang, X; Patacsil, D; Keller, CA; Giardine, B; mouse, EC; Kundaje, A; Wang, T; Pennacchio, LA; Weng, Z; Hardison, RC; Snyder, MP
  • The Next generation of risk assessment multi-year study-highlights of findings, applications to risk assessment, and future directions
    Cote, I; Andersen, ME; Ankley, GT; Barone, S; Birnbaum, LS; Boekelheide, K; Bois, FY; Burgoon, LD; Chiu, WA; Crawford-Brown, D; Crofton, KM; DeVito, M; Devlin, RB; Edwards, SW; Guyton, KZ; Hattis, D; Judson, RS; Knight, D; Krewski, D; Lambert, J; Maull, EA; Mendrick, D; Paoli, GM; Patel, CJ; Perkins, EJ; Poje, G; Portier, CJ; Rusyn, I; Schulte, PA; Simeonov, A; Smith, MT; Thayer, KA; Thomas, RS; Thomas, R; Tice, RR; Vandenberg, JJ; Villeneuve, DL; Wesselkamper, S; Whelan, M; Whittaker, C; White, R; Xia, M; Yauk, C; Zeise, L; Zhao, J; DeWoskin, RS
  • An integrated encyclopedia of DNA elements in the human genome
  • Exploring regulation in tissues with eQTL networks
    Fagny, M; Paulson, JN; Kuijjer, ML; Sonawane, AR; Chen, CY; Lopes-Ramos, CM; Glass, K; Quackenbush, J; Platig, J
  • Molecular dosimetry of 1,2,3,4-diepoxybutane-induced DNA-DNA cross-links in B6C3F1 mice and F344 rats exposed to 1,3-butadiene by inhalation
    Goggin, M; Swenberg, JA; Walker, VE; Tretyakova, N
  • Persistence and repair of bifunctional DNA adducts in tissues of laboratory animals exposed to 1,3-butadiene by inhalation
    Goggin, M; Sangaraju, D; Walker, VE; Wickliffe, J; Swenberg, JA; Tretyakova, N
  • Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans
  • circlize Implements and enhances circular visualization in R
    Gu, Z; Gu, L; Eils, R; Schlesner, M; Brors, B
  • New rodent population models may inform human health risk assessment and identification of genetic susceptibility to environmental exposures
    Harrill, AH; McAllister, KA
  • Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel
    Harrill, AH; Ross, PK; Gatti, DM; Threadgill, DW; Rusyn, I
  • Toxicology and epidemiology of 1,3-butadiene
    Himmelstein, MW; Acquavella, JF; Recio, L; Medinsky, MA; Bond, JA
  • IARC monographs on the evaluation of carcinogenic risks to humans. Volume97. 1,3-butadiene, ethylene oxide and vinyl halides (vinyl fluoride, vinyl chloride and vinyl bromide)
  • Chemical agents and related occupations—a review of human carcinogens
  • Oxidation of 3-butene-1,2-diol by alcohol dehydrogenase
    Kemper, RA; Elfarra, AA
  • Epigenetic mechanisms of mouse interstrain variability in genotoxicity of the environmental toxicant 1,3-butadiene
    Koturbash, I; Scherhag, A; Sorrentino, J; Sexton, K; Bodnar, W; Swenberg, JA; Beland, FA; Pardo-Manuel Devillena, F; Rusyn, I; Pogribny, IP
  • Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene
    Koturbash, I; Scherhag, A; Sorrentino, J; Sexton, K; Bodnar, W; Tryndyak, V; Latendresse, JR; Swenberg, JA; Beland, FA; Pogribny, IP; Rusyn, I
  • Chromatin immunoprecipitation and microarray-based analysis of protein location
    Lee, TI; Johnstone, SE; Young, RA
  • Genetic and epigenetic determinants of inter-individual variability in responses to toxicants
    Lewis, L; Crawford, GE; Furey, TS; Rusyn, I
  • RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
    Li, B; Dewey, CN
  • Comparison of the transcriptional landscapes between human and mouse tissues
    Lin, S; Lin, Y; Nery, JR; Urich, MA; Breschi, A; Davis, CA; Dobin, A; Zaleski, C; Beer, MA; Chapman, WC; Gingeras, TR; Ecker, JR; Snyder, MP
  • csaw: a Bioconductor package for differential binding analysis of ChIP-seq data using sliding windows
    Lun, AT; Smyth, GK
  • Cutadapt removes adapter sequences from high-throughput sequencing reads
    Martin, M
  • GREAT improves functional interpretation of cis-regulatory regions
    McLean, CY; Bristor, D; Hiller, M; Clarke, SL; Schaar, BT; Lowe, CB; Wenger, AM; Bejerano, G
  • 1,3-Butadiene induces cancer in experimental animals at all concentrations from 6.25 to 8000 parts per million
    Melnick, RL; Huff, JE
  • Age-, gender-, and species-dependent mutagenicity in T cells of mice and rats exposed by inhalation to 1,3-butadiene
    Meng, Q; Walker, DM; McDonald, JD; Henderson, RF; Carter, MM; Cook, DL; McCash, CL; Torres, SM; Bauer, MJ; Seilkop, SK; Upton, PB; Georgieva, NI; Boysen, G; Swenberg, JA; Walker, VE
  • Enrichment map: a network-based method for gene-set enrichment visualization and interpretation
    Merico, D; Isserlin, R; Stueker, O; Emili, A; Bader, GD
  • candidate risk factors and mechanisms for tolvaptan-induced liver injury are identified using a collaborative cross approach
    Mosedale, M; Kim, Y; Brock, WJ; Roth, SE; Wiltshire, T; Eaddy, JS; Keele, GR; Corty, RW; Xie, Y; Valdar, W; Watkins, PB
  • 1,3-Butadiene
  • Incomplete lung recovery following sub-acute inhalation of combustion-derived ultrafine particles in mice
    Noel, A; Xiao, R; Perveen, Z; Zaman, HM; Rouse, RL; Paulsen, DB; Penn, AL
  • Chloroprene: overview of studies under consideration for the development of an IRIS assessment
    Pagan, I
  • Environmental toxicants, epigenetics, and cancer
    Pogribny, IP; Rusyn, I
  • Integrative analysis of 111 reference human epigenomes
    Kundaje, A; Meuleman, W; Ernst, J; Bilenky, M; Yen, A; Heravi-Moussavi, A; Kheradpour, P; Zhang, Z; Wang, J; Ziller, MJ; Amin, V; Whitaker, JW; Schultz, MD; Ward, LD; Sarkar, A; Quon, G; Sandstrom, RS; Eaton, ML; Wu, YC; Pfenning, AR; Wang, X; Claussnitzer, M; Liu, Y; Coarfa, C; Harris, RA; Shoresh, N; Epstein, CB; Gjoneska, E; Leung, D; Xie, W; Hawkins, RD; Lister, R; Hong, C; Gascard, P; Mungall, AJ; Moore, R; Chuah, E; Tam, A; Canfield, TK; Hansen, RS; Kaul, R; Sabo, PJ; Bansal, MS; Carles, A; Dixon, JR; Farh, KH; Feizi, S; Karlic, R; Kim, AR; Kulkarni, A; Li, D; Lowdon, R; Elliott, G; Mercer, TR; Neph, SJ; Onuchic, V; Polak, P; Rajagopal, N; Ray, P; Sallari, RC; Siebenthall, KT; Sinnott-Armstrong, NA; Stevens, M; Thurman, RE; Wu, J; Zhang, B; Zhou, X; Beaudet, AE; Boyer, LA; Jager, PL; Farnham, PJ; Fisher, SJ; Haussler, D; Jones, SJ; Li, W; Marra, MA; McManus, MT; Sunyaev, S; Thomson, JA; Tlsty, TD; Tsai, LH; Wang, W; Waterland, RA; Zhang, MQ; Chadwick, LH; Bernstein, BE; Costello, JF; Ecker, JR; Hirst, M; Meissner, A; Milosavljevic, A; Ren, B; Stamatoyannopoulos, JA; Wang, T; Kellis, M
  • edgeR: a Bioconductor package for differential expression analysis of digital gene expression data
    Robinson, MD; McCarthy, DJ; Smyth, GK
  • Epigenomics: roadmap for regulation
    Romanoski, CE; Glass, CK; Stunnenberg, HG; Wilson, L; Almouzni, G
  • Toxicogenetics: population-based testing of drug and chemical safety in mouse models
    Rusyn, I
  • 1,3-Butadiene: biomarkers and application to risk assessment
    Swenberg, JA; Bordeerat, NK; Boysen, G; Carro, S; Georgieva, NI; Nakamura, J; Troutman, JM; Upton, PB; Albertini, RJ; Vacek, PM; Walker, VE; Sram, RJ; Goggin, M; Tretyakova, N
  • Cross-species transcriptomic analysis of mouse and rat lung exposed to chloroprene
    Thomas, RS; Himmelstein, MW; Clewell, HJ; Yang, Y; Healy, E; Black, MB; Andersen, ME
  • The accessible chromatin landscape of the human genome
    Thurman, RE; Rynes, E; Humbert, R; Vierstra, J; Maurano, MT; Haugen, E; Sheffield, NC; Stergachis, AB; Wang, H; Vernot, B; Garg, K; John, S; Sandstrom, R; Bates, D; Boatman, L; Canfield, TK; Diegel, M; Dunn, D; Ebersol, AK; Frum, T; Giste, E; Johnson, AK; Johnson, EM; Kutyavin, T; Lajoie, B; Lee, BK; Lee, K; London, D; Lotakis, D; Neph, S; Neri, F; Nguyen, ED; Qu, H; Reynolds, AP; Roach, V; Safi, A; Sanchez, ME; Sanyal, A; Shafer, A; Simon, JM; Song, L; Vong, S; Weaver, M; Yan, Y; Zhang, Z; Zhang, Z; Lenhard, B; Tewari, M; Dorschner, MO; Hansen, RS; Navas, PA; Stamatoyannopoulos, G; Iyer, VR; Lieb, JD; Sunyaev, SR; Akey, JM; Sabo, PJ; Kaul, R; Furey, TS; Dekker, J; Crawford, GE; Stamatoyannopoulos, JA
  • Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods
    Varemo, L; Nielsen, J; Nookaew, I
  • Fast and SNP-tolerant detection of complex variants and splicing in short reads
    Wu, TD; Nacu, S
  • A comparative encyclopedia of DNA elements in the mouse genome
    Yue, F; Cheng, Y; Breschi, A; Vierstra, J; Wu, W; Ryba, T; Sandstrom, R; Ma, Z; Davis, C; Pope, BD; Shen, Y; Pervouchine, DD; Djebali, S; Thurman, RE; Kaul, R; Rynes, E; Kirilusha, A; Marinov, GK; Williams, BA; Trout, D; Amrhein, H; Fisher-Aylor, K; Antoshechkin, I; DeSalvo, G; See, LH; Fastuca, M; Drenkow, J; Zaleski, C; Dobin, A; Prieto, P; Lagarde, J; Bussotti, G; Tanzer, A; Denas, O; Li, K; Bender, MA; Zhang, M; Byron, R; Groudine, MT; McCleary, D; Pham, L; Ye, Z; Kuan, S; Edsall, L; Wu, YC; Rasmussen, MD; Bansal, MS; Kellis, M; Keller, CA; Morrissey, CS; Mishra, T; Jain, D; Dogan, N; Harris, RS; Cayting, P; Kawli, T; Boyle, AP; Euskirchen, G; Kundaje, A; Lin, S; Lin, Y; Jansen, C; Malladi, VS; Cline, MS; Erickson, DT; Kirkup, VM; Learned, K; Sloan, CA; Rosenbloom, KR; Lacerda de Sousa, B; Beal, K; Pignatelli, M; Flicek, P; Lian, J; Kahveci, T; Lee, D; Kent, WJ; Ramalho Santos, M; Herrero, J; Notredame, C; Johnson, A; Vong, S; Lee, K; Bates, D; Neri, F; Diegel, M; Canfield, T; Sabo, PJ; Wilken, MS; Reh, TA; Giste, E; Shafer, A; Kutyavin, T; Haugen, E; Dunn, D; Reynolds, AP; Neph, S; Humbert, R; Hansen, RS; Bruijn, M; Selleri, L; Rudensky, A; Josefowicz, S; Samstein, R; Eichler, EE; Orkin, SH; Levasseur, D; Papayannopoulou, T; Chang, KH; Skoultchi, A; Gosh, S; Disteche, C; Treuting, P; Wang, Y; Weiss, MJ; Blobel, GA; Cao, X; Zhong, S; Wang, T; Good, PJ; Lowdon, RF; Adams, LB; Zhou, XQ; Pazin, MJ; Feingold, EA; Wold, B; Taylor, J; Mortazavi, A; Weissman, SM; Stamatoyannopoulos, JA; Snyder, MP; Guigo, R; Gingeras, TR; Gilbert, DM; Hardison, RC; Beer, MA; Ren, B; Mouse, EC
  • High-resolution mapping of open chromatin in the rice genome
    Zhang, W; Wu, Y; Schnable, JC; Zeng, Z; Freeling, M; Crawford, GE; Jiang, J

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