title: Back to the future: transgenerational transmission of xenobiotic-induced epigenetic remodeling.
abstract: Epigenetics, or regulation of gene expression independent of DNA sequence, is the missing link between genotype and phenotype. Epigenetic memory, mediated by histone and DNA modifications, is controlled by a set of specialized enzymes, metabolite availability, and signaling pathways. A mostly unstudied subject is how sub-toxic exposure to several xenobiotics during specific developmental stages can alter the epigenome and contribute to the development of disease phenotypes later in life. Furthermore, it has been shown that exposure to low-dose xenobiotics can also result in further epigenetic remodeling in the germ line and contribute to increase disease risk in the next generation (multigenerational and transgenerational effects). We here offer a perspective on current but still incomplete knowledge of xenobiotic-induced epigenetic alterations, and their possible transgenerational transmission. We also propose several molecular mechanisms by which the epigenetic landscape may be altered by environmental xenobiotics and hypothesize how diet and physical activity may counteract epigenetic alterations.
authors.affiliation: a Endocrine Division ; Hospital Sant Joan de Déu ; Esplugues de Llobregat , Barcelona , Spain.
authors.forename: Josep C
authors.initials: JC
authors.lastname: Jiménez-Chillarón
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Nijland
authors.forename: António A
authors.initials: AA
authors.lastname: Ascensão
authors.forename: Vilma A
authors.initials: VA
authors.lastname: Sardão
authors.forename: José
authors.initials: J
authors.lastname: Magalhães
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hitchler
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
mesh_terms: D042002:Chromatin Assembly and Disassembly; D002658:Developmental Disabilities / Q000209:etiology*; D004032:Diet; D004781:Environmental Exposure / Q000009:adverse effects; D044127:Epigenesis, Genetic; D005838:Genotype; D006801:Humans; D010641:Phenotype; D015262:Xenobiotics / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D015262:Xenobiotics
keywords: circadian clock; epigenetics; metabolism; toxicology; transgenerational effects