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@ARTICLE{Bauer:125485,
author = {T. Bauer$^*$ and S. Trump and N. Ishaque$^*$ and L.
Thürmann and L. Gu and M. Bauer and M. Bieg$^*$ and Z.
Gu$^*$ and D. Weichenhan$^*$ and J.-P. Mallm$^*$ and S.
Röder and G. Herberth and E. Takada and O. Mücke$^*$ and
M. Winter and K. M. Junge and K. Grützmann and U.
Rolle-Kampczyk and Q. Wang$^*$ and C. Lawerenz$^*$ and M.
Borte and T. Polte and M. Schlesner$^*$ and M. Schanne$^*$
and S. Wiemann$^*$ and C. Geörg$^*$ and H. G. Stunnenberg
and C. Plass$^*$ and K. Rippe$^*$ and J. Mizuguchi and C.
Herrmann$^*$ and R. Eils$^*$ and I. Lehmann},
title = {{E}nvironment-induced epigenetic reprogramming in genomic
regulatory elements in smoking mothers and their children.},
journal = {Molecular systems biology},
volume = {12},
number = {3},
issn = {1744-4292},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2017-01611},
pages = {861},
year = {2016},
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 = {Chromatin (NLM Chemicals) / Histones (NLM Chemicals) /
Mitogen-Activated Protein Kinase 9 (NLM Chemicals)},
cin = {B080 / C010 / W190 / W110 / B050 / B066},
ddc = {570},
cid = {I:(DE-He78)B080-20160331 / I:(DE-He78)C010-20160331 /
I:(DE-He78)W190-20160331 / I:(DE-He78)W110-20160331 /
I:(DE-He78)B050-20160331 / I:(DE-He78)B066-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27013061},
pmc = {pmc:PMC4812527},
url = {https://inrepo02.dkfz.de/record/125485},
}