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

Epigenomics. 2012 Feb;4(1):101-12. doi: 10.2217/epi.11.110.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CpG Islands
  • DNA Methylation
  • Environmental Pollutants / toxicity*
  • Epigenesis, Genetic
  • Female
  • HEK293 Cells
  • Histones / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Methylation
  • Polychlorinated Biphenyls / toxicity*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism*
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Transcription, Genetic

Substances

  • Environmental Pollutants
  • Histones
  • Receptors, Androgen
  • Polychlorinated Biphenyls
  • Jumonji Domain-Containing Histone Demethylases
  • Sirtuin 1