Skip to main content
SpringerLink
Log in

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

  • Published:
Mammalian Genome Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Boyle AP, Guinney J, Crawford GE, Furey TS (2008) F-Seq: a feature density estimator for high-throughput sequence tags. Bioinformatics 24:2537–2538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 (2011) Interstrain differences in the liver effects of trichloroethylene in a multistrain panel of inbred mice. Toxicol Sci 120:206–217

    Article  CAS  PubMed  Google Scholar 

  • Chappell G, Kobets T, O’Brien B, Tretyakova N, Sangaraju D, Kosyk O, Sexton KG, Bodnar W, Pogribny IP, Rusyn I (2014) Epigenetic events determine tissue-specific toxicity of inhalational exposure to the genotoxic chemical 1,3-butadiene in male C57BL/6J mice. Toxicol Sci 142:375–384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chappell G, Pogribny IP, Guyton KZ, Rusyn I (2016) Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: a systematic literature review. Mutat Res Rev Mutat Res 768:27–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chappell GA, Israel JW, Simon JM, Pott S, Safi A, Eklund K, Sexton KG, Bodnar W, Lieb JD, Crawford GE, Rusyn I, Furey TS (2017) 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. Environ Health Perspect 125:107006

    Article  PubMed  Google Scholar 

  • 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 (2014) Principles of regulatory information conservation between mouse and human. Nature 515:371–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 (2016) The Next generation of risk assessment multi-year study-highlights of findings, applications to risk assessment, and future directions. Environ Health Perspect 124:1671–1682

    Article  PubMed  PubMed Central  Google Scholar 

  • Encode Project Consortium, Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee BK, Pauli F, Rosenbloom KR, Sabo P, Safi A, Sanyal A, Shoresh N, Simon JM, Song L, Trinklein ND, Altshuler RC, Birney E, Brown JB, Cheng C, Djebali S, Dong X, Dunham I, Ernst J, Furey TS, Gerstein M, Giardine B, Greven M, Hardison RC, Harris RS, Herrero J, Hoffman MM, Iyer S, Kelllis M, Khatun J, Kheradpour P, Kundaje A, Lassman T, Li Q, Lin X, Marinov GK, Merkel A, Mortazavi A, Parker SC, Reddy TE, Rozowsky J, Schlesinger F, Thurman RE, Wang J, Ward LD, Whitfield TW, Wilder SP, Wu W, Xi HS, Yip KY, Zhuang J, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M, Pazin MJ, Lowdon RF, Dillon LA, Adams LB, Kelly CJ, Zhang J, Wexler JR, Green ED, Good PJ, Feingold EA, Bernstein BE, Birney E, Crawford GE, Dekker J, Elinitski L, Farnham PJ, Gerstein M, Giddings MC, Gingeras TR, Green ED, Guigo R, Hardison RC, Hubbard TJ, Kellis M, Kent WJ, Lieb JD, Margulies EH, Myers RM, Snyder M, Starnatoyannopoulos JA, Tennebaum SA, Weng Z, White KP, Wold B, Khatun J, Yu Y, Wrobel J, Risk BA, Gunawardena HP, Kuiper HC, Maier CW, Xie L, Chen X, Giddings MC, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Kheradpour P, Mikkelsen TS, Gillespie S, Goren A, Ram O, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Eaton ML, Kellis M, Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Roder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Batut P, Bell I, Bell K, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena HP, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Li G, Luo OJ, Park E, Preall JB, Presaud K, Ribeca P, Risk BA, Robyr D, Ruan X, Sammeth M, Sandu KS, Schaeffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Hayashizaki Y, Harrow J, Gerstein M, Hubbard TJ, Reymond A, Antonarakis SE, Hannon GJ, Giddings MC, Ruan Y, Wold B, Carninci P, Guigo R, Gingeras TR, Rosenbloom KR, Sloan CA, Learned K, Malladi VS, Wong MC, Barber GP, Cline MS, Dreszer TR, Heitner SG, Karolchik D, Kent WJ, Kirkup VM, Meyer LR, Long JC, Maddren M, Raney BJ, Furey TS, Song L, Grasfeder LL, Giresi PG, Lee BK, Battenhouse A, Sheffield NC, Simon JM, Showers KA, Safi A, London D, Bhinge AA, Shestak C, Schaner MR, Kim SK, Zhang ZZ, Mieczkowski PA, Mieczkowska JO, Liu Z, McDaniell RM, Ni Y, Rashid NU, Kim MJ, Adar S, Zhang Z, Wang T, Winter D, Keefe D, Birney E, Iyer VR, Lieb JD, Crawford GE, Li G, Sandhu KS, Zheng M, Wang P, Luo OJ, Shahab A, Fullwood MJ, Ruan X, Ruan Y, Myers RM, Pauli F, Williams BA, Gertz J, Marinov GK, Reddy TE, Vielmetter J, Partridge EC, Trout D, Varley KE, Gasper C, Bansal A, Pepke S, Jain P, Amrhein H, Bowling KM, Anaya M, Cross MK, King B, Muratet MA, Antoshechkin I, Newberry KM, McCue K, Nesmith AS, Fisher-Aylor KI, Pusey B, DeSalvo G, Parker SL, Balasubramanian S, Davis NS, Meadows SK, Eggleston T, Gunter C, Newberry JS, Levy SE, Absher DM, Mortazavi A, Wong WH, Wold B, Blow MJ, Visel A, Pennachio LA, Elnitski L, Margulies EH, Parker SC, Petrykowska HM, Abyzov A, Aken B, Barrell D, Barson G, Berry A, Bignell A, Boychenko V, Bussotti G, Chrast J, Davidson C, Derrien T, Despacio-Reyes G, Diekhans M, Ezkurdia I, Frankish A, Gilbert J, Gonzalez JM, Griffiths E, Harte R, Hendrix DA, Howald C, Hunt T, Jungreis I, Kay M, Khurana E, Kokocinski F, Leng J, Lin MF, Loveland J, Lu Z, Manthravadi D, Mariotti M, Mudge J, Mukherjee G, Notredame C, Pei B, Rodriguez JM, Saunders G, Sboner A, Searle S, Sisu C, Snow C, Steward C, Tanzer A, Tapanan E, Tress ML, van Baren MJ, Walters N, Washieti S, Wilming L, Zadissa A, Zhengdong Z, Brent M, Haussler D, Kellis M, Valencia A, Gerstein M, Raymond A, Guigo R, Harrow J, Hubbard TJ, Landt SG, Frietze S, Abyzov A, Addleman N, Alexander RP, Auerbach RK, Balasubramanian S, Bettinger K, Bhardwaj N, Boyle AP, Cao AR, Cayting P, Charos A, Cheng Y, Cheng C, Eastman C, Euskirchen G, Fleming JD, Grubert F, Habegger L, Hariharan M, Harmanci A, Iyenger S, Jin VX, Karczewski KJ, Kasowski M, Lacroute P, Lam H, Larnarre-Vincent N, Leng J, Lian J, Lindahl-Allen M, Min R, Miotto B, Monahan H, Moqtaderi Z, Mu XJ, O’Geen H, Ouyang Z, Patacsil D, Pei B, Raha D, Ramirez L, Reed B, Rozowsky J, Sboner A, Shi M, Sisu C, Slifer T, Witt H, Wu L, Xu X, Yan KK, Yang X, Yip KY, Zhang Z, Struhl K, Weissman SM, Gerstein M, Farnham PJ, Snyder M, Tenebaum SA, Penalva LO, Doyle F, Karmakar S, Landt SG, Bhanvadia RR, Choudhury A, Domanus M, Ma L, Moran J, Patacsil D, Slifer T, Victorsen A, Yang X, Snyder M, White KP, Auer T, Centarin L, Eichenlaub M, Gruhl F, Heerman S, Hoeckendorf B, Inoue D, Kellner T, Kirchmaier S, Mueller C, Reinhardt R, Schertel L, Schneider S, Sinn R, Wittbrodt B, Wittbrodt J, Weng Z, Whitfield TW, Wang J, Collins PJ, Aldred SF, Trinklein ND, Partridge EC, Myers RM, Dekker J, Jain G, Lajoie BR, Sanyal A, Balasundaram G, Bates DL, Byron R, Canfield TK, Diegel MJ, Dunn D, Ebersol AK, Ebersol AK, Frum T, Garg K, Gist E, Hansen RS, Boatman L, Haugen E, Humbert R, Jain G, Johnson AK, Johnson EM, Kutyavin TM, Lajoie BR, Lee K, Lotakis D, Maurano MT, Neph SJ, Neri FV, Nguyen ED, Qu H, Reynolds AP, Roach V, Rynes E, Sabo P, Sanchez ME, Sandstrom RS, Sanyal A, Shafer AO, Stergachis AB, Thomas S, Thurman RE, Vernot B, Vierstra J, Vong S, Wang H, Weaver MA, Yan Y, Zhang M, Akey JA, Bender M, Dorschner MO, Groudine M, MacCoss MJ, Navas P, Stamatoyannopoulos G, Kaul R, Dekker J, Stamatoyannopoulos JA, Dunham I, Beal K, Brazma A, Flicek P, Herrero J, Johnson N, Keefe D, Lukk M, Luscombe NM, Sobral D, Vaquerizas JM, Wilder SP, Batzoglou S, Sidow A, Hussami N, Kyriazopoulou-Panagiotopoulou S, Libbrecht MW, Schaub MA, Kundaje A, Hardison RC, Miller W, Giardine B, Harris RS, Wu W, Bickel PJ, Banfai B, Boley NP, Brown JB, Huang H, Li Q, Li JJ, Noble WS, Bilmes JA, Buske OJ, Hoffman MM, Sahu AO, Kharchenko PV, Park PJ, Baker D, Taylor J, Weng Z, Iyer S, Dong X, Greven M, Lin X, Wang J, Xi HS, Zhuang J, Gerstein M, Alexander RP, Balasubramanian S, Cheng C, Harmanci A, Lochovsky L, Min R, Mu XJ, Rozowsky J, Yan KK, Yip KY, Birney E (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74

    Article  Google Scholar 

  • Fagny M, Paulson JN, Kuijjer ML, Sonawane AR, Chen CY, Lopes-Ramos CM, Glass K, Quackenbush J, Platig J (2017) Exploring regulation in tissues with eQTL networks. Proc Natl Acad Sci USA 114:E7841-E7850

    Article  PubMed  PubMed Central  Google Scholar 

  • Goggin M, Swenberg JA, Walker VE, Tretyakova N (2009) 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. Cancer Res 69:2479–2486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goggin M, Sangaraju D, Walker VE, Wickliffe J, Swenberg JA, Tretyakova N (2011) Persistence and repair of bifunctional DNA adducts in tissues of laboratory animals exposed to 1,3-butadiene by inhalation. Chem Res Toxicol 24:809–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • GTEx Consortium (2015) Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348, 648–660

    Article  PubMed Central  Google Scholar 

  • Gu Z, Gu L, Eils R, Schlesner M, Brors B (2014) circlize Implements and enhances circular visualization in R. Bioinformatics 30:2811–2812

    Article  CAS  PubMed  Google Scholar 

  • Harrill AH, McAllister KA (2017) New rodent population models may inform human health risk assessment and identification of genetic susceptibility to environmental exposures. Environ Health Perspect 125:086002

    Article  PubMed  PubMed Central  Google Scholar 

  • Harrill AH, Ross PK, Gatti DM, Threadgill DW, Rusyn I (2009) Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel. Toxicol Sci 110:235–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Himmelstein MW, Acquavella JF, Recio L, Medinsky MA, Bond JA (1997) Toxicology and epidemiology of 1,3-butadiene. Crit Rev Toxicol 27:1–108

    Article  CAS  PubMed  Google Scholar 

  • IARC (2008) IARC monographs on the evaluation of carcinogenic risks to humans. Volume 97. 1,3-butadiene, ethylene oxide and vinyl halides (vinyl fluoride, vinyl chloride and vinyl bromide). IARC Monogr Eval Carcinog Risks Hum 97, 3–471

    Google Scholar 

  • IARC (2012) Chemical agents and related occupations—a review of human carcinogens. IARC Monogr Eval Carcinog Risks Hum 100F, 1–567

    Google Scholar 

  • Kemper RA, Elfarra AA (1996) Oxidation of 3-butene-1,2-diol by alcohol dehydrogenase. Chem Res Toxicol 9:1127–1134

    Article  CAS  PubMed  Google Scholar 

  • Koturbash I, Scherhag A, Sorrentino J, Sexton K, Bodnar W, Swenberg JA, Beland FA, Pardo-Manuel Devillena F, Rusyn I, Pogribny IP (2011a) Epigenetic mechanisms of mouse interstrain variability in genotoxicity of the environmental toxicant 1,3-butadiene. Toxicol Sci 122:448–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koturbash I, Scherhag A, Sorrentino J, Sexton K, Bodnar W, Tryndyak V, Latendresse JR, Swenberg JA, Beland FA, Pogribny IP, Rusyn I (2011b) Epigenetic alterations in liver of C57BL/6J mice after short-term inhalational exposure to 1,3-butadiene. Environ Health Perspect 119:635–640

    Article  CAS  PubMed  Google Scholar 

  • Lee TI, Johnstone SE, Young RA (2006) Chromatin immunoprecipitation and microarray-based analysis of protein location. Nat Protoc 1:729–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis L, Crawford GE, Furey TS, Rusyn I (2017) Genetic and epigenetic determinants of inter-individual variability in responses to toxicants. Curr Opin Toxicol 6:50–59

    Article  PubMed  Google Scholar 

  • Li B, Dewey CN (2011) RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12:323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 (2014) Comparison of the transcriptional landscapes between human and mouse tissues. Proc Natl Acad Sci USA 111:17224–17229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lun AT, Smyth GK (2016) csaw: a Bioconductor package for differential binding analysis of ChIP-seq data using sliding windows. Nucleic Acids Res 44:e45

    Article  PubMed  Google Scholar 

  • Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet.journal 17:10–12

    Article  Google Scholar 

  • McLean CY, Bristor D, Hiller M, Clarke SL, Schaar BT, Lowe CB, Wenger AM, Bejerano G (2010) GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol 28:495–501

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Melnick RL, Huff JE (1993) 1,3-Butadiene induces cancer in experimental animals at all concentrations from 6.25 to 8000 parts per million. IARC Sci Publ 127:309–322

    CAS  Google Scholar 

  • Meng Q, Walker DM, McDonald JD, Henderson RF, Carter MM, Cook DL Jr, McCash CL, Torres SM, Bauer MJ, Seilkop SK, Upton PB, Georgieva NI, Boysen G, Swenberg JA, Walker VE (2007) Age-, gender-, and species-dependent mutagenicity in T cells of mice and rats exposed by inhalation to 1,3-butadiene. Chem Biol Interact 166:121–131

    Article  CAS  PubMed  Google Scholar 

  • Merico D, Isserlin R, Stueker O, Emili A, Bader GD (2010) Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS ONE 5:e13984

    Article  PubMed  PubMed Central  Google Scholar 

  • Mosedale M, Kim Y, Brock WJ, Roth SE, Wiltshire T, Eaddy JS, Keele GR, Corty RW, Xie Y, Valdar W, Watkins PB (2017) candidate risk factors and mechanisms for tolvaptan-induced liver injury are identified using a collaborative cross approach. Toxicol Sci 156:438–454

    CAS  PubMed  Google Scholar 

  • National Toxicology Program (2011) 1,3-Butadiene. Rep Carcinog 12:75–77

    Google Scholar 

  • Noel A, Xiao R, Perveen Z, Zaman HM, Rouse RL, Paulsen DB, Penn AL (2016) Incomplete lung recovery following sub-acute inhalation of combustion-derived ultrafine particles in mice. Part Fibre Toxicol 13:10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pagan I (2007) Chloroprene: overview of studies under consideration for the development of an IRIS assessment. Chem Biol Interact 166:341–351

    Article  CAS  PubMed  Google Scholar 

  • Pogribny IP, Rusyn I (2013) Environmental toxicants, epigenetics, and cancer. Adv Exp Med Biol 754:215–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roadmap Epigenomics Consortium, 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, De 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 (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330

    Article  PubMed Central  Google Scholar 

  • Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26:139–140

    Article  CAS  PubMed  Google Scholar 

  • Romanoski CE, Glass CK, Stunnenberg HG, Wilson L, Almouzni G (2015) Epigenomics: roadmap for regulation. Nature 518:314–316

    Article  CAS  PubMed  Google Scholar 

  • Rusyn I (2010) Toxicogenetics: population-based testing of drug and chemical safety in mouse models. Mutat Res 11:1127–1136

    CAS  Google Scholar 

  • 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 (2011) 1,3-Butadiene: biomarkers and application to risk assessment. Chem Biol Interact 24:809–817

    Google Scholar 

  • Thomas RS, Himmelstein MW, Clewell HJ 3rd, Yang Y, Healy E, Black MB, Andersen ME (2013) Cross-species transcriptomic analysis of mouse and rat lung exposed to chloroprene. Toxicol Sci 131:629–640

    Article  CAS  PubMed  Google Scholar 

  • 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 (2012) The accessible chromatin landscape of the human genome. Nature 489:75–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Varemo L, Nielsen J, Nookaew I (2013) Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods. Nucleic Acids Res 41:4378–4391

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu TD, Nacu S (2010) Fast and SNP-tolerant detection of complex variants and splicing in short reads. Bioinformatics 26:873–881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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, De 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 (2014) A comparative encyclopedia of DNA elements in the mouse genome. Nature 515:355–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang W, Wu Y, Schnable JC, Zeng Z, Freeling M, Crawford GE, Jiang J (2012) High-resolution mapping of open chromatin in the rice genome. Genome Res 22:151–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported, in part, by grants from National Institutes of Health (NIH R01ES023195 and P30ES025128). The views expressed in this article are those of the authors and do not necessarily reflect the views of NIH.

Data Access

All RNA-seq, ATAC-seq, and ChIP-seq data sets generated during this study have been submitted to the NCBI Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo/, accession GSE108990).

Author information

Authors and Affiliations

  1. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    Jennifer W. Israel, Jeremy M. Simon, Paul Cotney & Terrence S. Furey

  2. Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA

    Grace A. Chappell, Lauren Lewis & Ivan Rusyn

  3. Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA

    Grace A. Chappell & Wanda Bodnar

  4. Department of Human Genetics, University of Chicago, Chicago, IL, USA

    Sebastian Pott, Hala S. Boulos & Jason D. Lieb

  5. Department of Pediatrics, Duke Center for Genomic and Computational Biology, Duke University, Durham, NC, USA

    Alexias Safi & Gregory E. Crawford

  6. Department of Biology, University of North Carolina, Chapel Hill, NC, USA

    Terrence S. Furey

  7. UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Terrence S. Furey

Authors
  1. Jennifer W. Israel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Grace A. Chappell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeremy M. Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sebastian Pott
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexias Safi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lauren Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Cotney
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hala S. Boulos
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wanda Bodnar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jason D. Lieb
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gregory E. Crawford
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Terrence S. Furey
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ivan Rusyn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Terrence S. Furey or Ivan Rusyn.

Ethics declarations

Conflict of interest

G. Chappell is currently employed by ToxStrategies, Inc., a scientific consulting firm. G. Chappell received no funding from ToxStrategies or any of its clients for this project, nor was ToxStrategies or any of its clients involved in the development or execution of the research presented herein. The other authors declare that they have no actual or potential competing financial interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Israel, J.W., Chappell, G.A., Simon, J.M. et al. Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription. Mamm Genome 29, 153–167 (2018). https://doi.org/10.1007/s00335-018-9739-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-018-9739-6

Keywords

Search

Navigation