Epigenetic regulation of ABCG2 gene is associated with susceptibility to xenobiotic exposure

Journal of Proteomics
Kavitha BabuAllan M Sheppard

Abstract

A highly conserved defence mechanism has evolved to protect cells from oxidative stress and xenobiotic exposure. A network of coupled xenobiotic metabolizing enzymatic reactions (XMEs) converts free oxidative radicals to less damaging metabolites, while efflux pumps remove toxins and XME derivatives from the cell. These mechanisms have been well studied in the contexts of hypoxia and Multidrug Resistance (MDR). Exposure of ruminants to fungal toxins leads to hepatotoxicosis and subsequent skin eczema (FE) depending upon toxic burden. Using toxin challenge in sheep we have investigated the potential for epigenetic regulation in cellular responses to xenobiotic exposure with a focus on the efflux protein ABCG2 which functions in Phase III of the defence mechanism. We show that 'resistance' to FE disease is positively associated with ABCG2 expression, and inversely correlated with DNA methylation state at CpG sites in the regulatory region of the ABCG2 gene. The analytical sensitivity provided by the Sequenom EpiTyper MS platform allows resolution of individual CpG sites varying significantly with disease progression, informing fine mapping of relevant transcription factor bindings which underpin this epigenetic response. Our find...Continue Reading

References

Apr 1, 1978·New Zealand Veterinary Journal·N R Towers, G C Stratton
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·L A DoyleD D Ross
Sep 1, 1999·Animal Genetics·S H PhuaA M Crawford
Mar 27, 2004·The Journal of Biological Chemistry·Partha KrishnamurthyJohn D Schuetz
Jul 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Hitomi Nishio, Martin J Walsh
Jul 21, 2005·New Zealand Veterinary Journal·B L Smith
Sep 15, 2005·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Partha Krishnamurthy, John D Schuetz
Jan 25, 2006·Proceedings of the National Academy of Sciences of the United States of America·Serge SaxonovDouglas L Brutlag
May 9, 2008·Nature Reviews. Genetics·Miho M Suzuki, Adrian Bird
Mar 25, 2009·Nature Reviews. Genetics·Howard Cedar, Yehudit Bergman
Apr 21, 2009·Nature Structural & Molecular Biology·Ravid StraussmanHoward Cedar
May 7, 2009·Biochimica Et Biophysica Acta·Paul T TarrAngel Baldán
Feb 4, 2010·Nature Reviews. Genetics·Peter W Laird
Dec 15, 2010·Biometrical Journal. Biometrische Zeitschrift·Chihiro HirotsuFrank Bretz

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Citations

Sep 23, 2014·Biochimica Et Biophysica Acta·Samriddhi Shukla, Syed Musthapa Meeran
Oct 23, 2014·Journal of Developmental Origins of Health and Disease·A B PleasantsA M Sheppard
Jun 28, 2019·Systems Biology in Reproductive Medicine·Panagiotis NtostisDavid Miller
May 24, 2017·International Journal of Oncology·Bao-Yuan HuangChang-Qing Zeng

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