TY  - JOUR
AU  - Bauer, Tobias
AU  - Trump, Saskia
AU  - Ishaque, Naveed
AU  - Thürmann, Loreen
AU  - Gu, Lei
AU  - Bauer, Mario
AU  - Bieg, Matthias
AU  - Gu, Zuguang
AU  - Weichenhan, Dieter
AU  - Mallm, Jan-Philipp
AU  - Röder, Stefan
AU  - Herberth, Gunda
AU  - Takada, Eiko
AU  - Mücke, Oliver
AU  - Winter, Marcus
AU  - Junge, Kristin M
AU  - Grützmann, Konrad
AU  - Rolle-Kampczyk, Ulrike
AU  - Wang, Qi
AU  - Lawerenz, Christian
AU  - Borte, Michael
AU  - Polte, Tobias
AU  - Schlesner, Matthias
AU  - Schanne, Michaela
AU  - Wiemann, Stefan
AU  - Geörg, Christina
AU  - Stunnenberg, Hendrik G
AU  - Plass, Christoph
AU  - Rippe, Karsten
AU  - Mizuguchi, Junichiro
AU  - Herrmann, Carl
AU  - Eils, Roland
AU  - Lehmann, Irina
TI  - Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children.
JO  - Molecular systems biology
VL  - 12
IS  - 3
SN  - 1744-4292
CY  - Heidelberg
PB  - EMBO Press
M1  - DKFZ-2017-01611
SP  - 861
PY  - 2016
AB  - 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.
KW  - Chromatin (NLM Chemicals)
KW  - Histones (NLM Chemicals)
KW  - Mitogen-Activated Protein Kinase 9 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27013061
C2  - pmc:PMC4812527
UR  - https://inrepo02.dkfz.de/record/125485
ER  -