title: Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation?
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, Pathophysiology & Applied Biology, INBB Research Unit, University of Milano, Milano, Italy. lavinia.casati@unimi.it
authors.forename: Lavinia
authors.initials: L
authors.lastname: Casati
authors.forename: Ramon
authors.initials: R
authors.lastname: Sendra
authors.forename: Alessandra
authors.initials: A
authors.lastname: Colciago
authors.forename: Paola
authors.initials: P
authors.lastname: Negri-Cesi
authors.forename: Maria
authors.initials: M
authors.lastname: Berdasco
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Fabio
authors.initials: F
authors.lastname: Celotti
mesh_terms: D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D004785:Environmental Pollutants / Q000633:toxicity*; D044127:Epigenesis, Genetic; D005260:Female; D057809:HEK293 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008745:Methylation; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004785:Environmental Pollutants; D006657:Histones; D011944:Receptors, Androgen; D011078:Polychlorinated Biphenyls; D056484:Jumonji Domain-Containing Histone Demethylases; D056564:Sirtuin 1