Background: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen receptor (AR), function as coregulators of histone modification enzymes. Aim: To clarify if a PCB early-life exposure might affect the epigenome in rat liver, we analyzed some histone post-translational modifications (H3K4me3 and H4K16Ac) and the corresponding histone remodeling enzymes, and the AR as a histone enzyme coregulator. Results: We observed a decrease of H4K16Ac and H3K4me3 levels, possibly linked to the induction of chromatin-modifying enzymes SirtT1 and Jarid1b, and a decrease of AR. PCBs also seem to induce AR transcriptional activity. Some of the observed effects are sex dimorphic. Conclusion: Our data suggest that an early-life exposure to PCB sometimes modifies the epigenome in the offspring liver in a dimorphic way. AR might be involved in modulating PCB effects on the epigenome.

Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation? / L. Casati, R. Sendra, A. Colciago, P. Negri-Cesi, M. Berdasco, M. Esteller, F.M. Celotti. - In: EPIGENOMICS. - ISSN 1750-1911. - 4:1(2012 Feb), pp. 101-112.

Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation?

L. Casati
;
A. Colciago;P. Negri-Cesi;F.M. Celotti
Ultimo
2012

Abstract

Background: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen receptor (AR), function as coregulators of histone modification enzymes. Aim: To clarify if a PCB early-life exposure might affect the epigenome in rat liver, we analyzed some histone post-translational modifications (H3K4me3 and H4K16Ac) and the corresponding histone remodeling enzymes, and the AR as a histone enzyme coregulator. Results: We observed a decrease of H4K16Ac and H3K4me3 levels, possibly linked to the induction of chromatin-modifying enzymes SirtT1 and Jarid1b, and a decrease of AR. PCBs also seem to induce AR transcriptional activity. Some of the observed effects are sex dimorphic. Conclusion: Our data suggest that an early-life exposure to PCB sometimes modifies the epigenome in the offspring liver in a dimorphic way. AR might be involved in modulating PCB effects on the epigenome.
androgen receptor; endocrine disruptors; epigenetics; histone modifications; Jarid1b; polychlorinated biphenyls
Settore MED/04 - Patologia Generale
Settore BIO/09 - Fisiologia
feb-2012
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/169684
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