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

Publication ,  Journal Article
Israel, JW; Chappell, GA; Simon, JM; Pott, S; Safi, A; Lewis, L; Cotney, P; Boulos, HS; Bodnar, W; Lieb, JD; Crawford, GE; Furey, TS; Rusyn, I
Published in: Mamm Genome
February 2018

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.

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Published In

Mamm Genome

DOI

EISSN

1432-1777

Publication Date

February 2018

Volume

29

Issue

1-2

Start / End Page

153 / 167

Location

United States

Related Subject Headings

  • Transcriptome
  • Transcription, Genetic
  • Organ Specificity
  • Mutagenicity Tests
  • Mice
  • Lung
  • Liver
  • Histones
  • Genetics & Heredity
  • Epigenesis, Genetic
 

Citation

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Israel, J. W., Chappell, G. A., Simon, J. M., Pott, S., Safi, A., Lewis, L., … Rusyn, I. (2018). Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription. Mamm Genome, 29(1–2), 153–167. https://doi.org/10.1007/s00335-018-9739-6
Israel, Jennifer W., Grace A. Chappell, Jeremy M. Simon, Sebastian Pott, Alexias Safi, Lauren Lewis, Paul Cotney, et al. “Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription.Mamm Genome 29, no. 1–2 (February 2018): 153–67. https://doi.org/10.1007/s00335-018-9739-6.
Israel JW, Chappell GA, Simon JM, Pott S, Safi A, Lewis L, et al. Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription. Mamm Genome. 2018 Feb;29(1–2):153–67.
Israel, Jennifer W., et al. “Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription.Mamm Genome, vol. 29, no. 1–2, Feb. 2018, pp. 153–67. Pubmed, doi:10.1007/s00335-018-9739-6.
Israel JW, Chappell GA, Simon JM, Pott S, Safi A, Lewis L, Cotney P, Boulos HS, Bodnar W, Lieb JD, Crawford GE, Furey TS, Rusyn I. Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription. Mamm Genome. 2018 Feb;29(1–2):153–167.
Journal cover image

Published In

Mamm Genome

DOI

EISSN

1432-1777

Publication Date

February 2018

Volume

29

Issue

1-2

Start / End Page

153 / 167

Location

United States

Related Subject Headings

  • Transcriptome
  • Transcription, Genetic
  • Organ Specificity
  • Mutagenicity Tests
  • Mice
  • Lung
  • Liver
  • Histones
  • Genetics & Heredity
  • Epigenesis, Genetic