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Mol Syst Biol. 2016 Mar 24;12(3):861. doi: 10.15252/msb.20156520.

Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children.

Author information

  • 1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 2Department of Environmental Immunology, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany.
  • 3Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Heidelberg Center for Personalized Oncology, DKFZ-HIPO, DKFZ, Heidelberg, Germany.
  • 4Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 5Research Group Genome Organization & Function, German Cancer Research Center (DKFZ) and Bioquant, Heidelberg, Germany.
  • 6Department of Immunology, Tokyo Medical University, Tokyo, Japan.
  • 7Department Metabolomics, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany.
  • 8Municipal Hospital "St Georg" Children's Hospital, Leipzig, Germany.
  • 9Department of Environmental Immunology, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany Department of Dermatology, Venerology and Allerology, Leipzig University Medical Center, Leipzig, Germany.
  • 10Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 11Sample Processing Lab, National Center for Tumor Disease and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 12Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
  • 13Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Institute of Pharmacy and Molecular Biotechnology and Bioquant Center, University of Heidelberg, Heidelberg, Germany.
  • 14Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Heidelberg Center for Personalized Oncology, DKFZ-HIPO, DKFZ, Heidelberg, Germany Institute of Pharmacy and Molecular Biotechnology and Bioquant Center, University of Heidelberg, Heidelberg, Germany Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany r.eils@dkfz-heidelberg.de irina.lehmann@ufz.de.
  • 15Department of Environmental Immunology, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany r.eils@dkfz-heidelberg.de irina.lehmann@ufz.de.

Abstract

Epigenetic mechanisms have emerged as links between prenatal environmental exposure and disease risk later in life. Here, we studied epigenetic changes associated with maternal smoking at base pair resolution by mapping DNA methylation, histone modifications, and transcription in expectant mothers and their newborn children. We found extensive global differential methylation and carefully evaluated these changes to separate environment associated from genotype-related DNA methylation changes. Differential methylation is enriched in enhancer elements and targets in particular "commuting" enhancers having multiple, regulatory interactions with distal genes. Longitudinal whole-genome bisulfite sequencing revealed that DNA methylation changes associated with maternal smoking persist over years of life. Particularly in children prenatal environmental exposure leads to chromatin transitions into a hyperactive state. Combined DNA methylation, histone modification, and gene expression analyses indicate that differential methylation in enhancer regions is more often functionally translated than methylation changes in promoters or non-regulatory elements. Finally, we show that epigenetic deregulation of a commuting enhancer targeting c-Jun N-terminal kinase 2 (JNK2) is linked to impaired lung function in early childhood.

KEYWORDS:

WGBS; enhancer deregulation; environment; epigenetics; histone modifications

PMID:
27013061
PMCID:
PMC4812527
[PubMed - indexed for MEDLINE]
Free PMC Article
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