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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

1
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Department of Environmental Immunology, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany.
3
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Heidelberg Center for Personalized Oncology, DKFZ-HIPO, DKFZ, Heidelberg, Germany.
4
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
Research Group Genome Organization & Function, German Cancer Research Center (DKFZ) and Bioquant, Heidelberg, Germany.
6
Department of Immunology, Tokyo Medical University, Tokyo, Japan.
7
Department Metabolomics, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany.
8
Municipal Hospital "St Georg" Children's Hospital, Leipzig, Germany.
9
Department of Environmental Immunology, Helmholtz Centre for Environmental Research Leipzig - UFZ, Leipzig, Germany Department of Dermatology, Venerology and Allerology, Leipzig University Medical Center, Leipzig, Germany.
10
Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
11
Sample Processing Lab, National Center for Tumor Disease and German Cancer Research Center (DKFZ), Heidelberg, Germany.
12
Department of Molecular Biology, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
13
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Institute of Pharmacy and Molecular Biotechnology and Bioquant Center, University of Heidelberg, Heidelberg, Germany.
14
Division 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.
15
Department 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
DOI:
10.15252/msb.20156520
[Indexed for MEDLINE]
Free PMC Article

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