PT - JOURNAL ARTICLE AU - Antonio Vitobello AU - Juliane Perner AU - Johanna Beil AU - Jiang Zhu AU - Alberto Del Río-Espínola AU - Laurent Morawiec AU - Magdalena Westphal AU - Valérie Dubost AU - Marc Altorfer AU - Ulrike Naumann AU - Arne Mueller AU - Karen Kapur AU - Mark Borowsky AU - Colin Henderson AU - C Roland Wolf AU - Michael Schwarz AU - Jonathan Moggs AU - Rémi Terranova TI - Drug-induced chromatin accessibility changes associate with sensitivity to liver tumor promotion AID - 10.26508/lsa.201900461 DP - 2019 Oct 01 TA - Life Science Alliance PG - e201900461 VI - 2 IP - 5 4099 - https://www.life-science-alliance.org/content/2/5/e201900461.short 4100 - https://www.life-science-alliance.org/content/2/5/e201900461.full SO - Life Sci. Alliance2019 Oct 01; 2 AB - Liver cancer susceptibility varies amongst humans and between experimental animal models because of multiple genetic and epigenetic factors. The molecular characterization of such susceptibilities has the potential to enhance cancer risk assessment of xenobiotic exposures and disease prevention strategies. Here, using DNase I hypersensitivity mapping coupled with transcriptomic profiling, we investigate perturbations in cis-acting gene regulatory elements associated with the early stages of phenobarbital (PB)-mediated liver tumor promotion in susceptible versus resistant mouse strains (B6C3F1 versus C57BL/6J). Integrated computational analyses of strain-selective changes in liver chromatin accessibility underlying PB response reveal differential epigenetic regulation of molecular pathways associated with PB-mediated tumor promotion, including Wnt/β-catenin signaling. Complementary transcription factor motif analyses reveal mouse strain–selective gene regulatory networks and a novel role for Stat, Smad, and Fox transcription factors in the early stages of PB-mediated tumor promotion. Mapping perturbations in cis-acting gene regulatory elements provides novel insights into the molecular basis for susceptibility to xenobiotic-induced rodent liver tumor promotion and has the potential to enhance mechanism-based cancer risk assessments of xenobiotic exposures.