Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children
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...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 March 2016
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| In: |
Molecular systems biology
Year: 2016, Volume: 12, Issue: 3 |
| ISSN: | 1744-4292 |
| DOI: | 10.15252/msb.20156520 |
| Online Access: | Verlag, Volltext: https://doi.org/10.15252/msb.20156520 Verlag, Volltext: https://www.embopress.org/doi/full/10.15252/msb.20156520 
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| Author Notes: | Tobias Bauer, Saskia Trump, Naveed Ishaque, Loreen Thürmann, Lei Gu, Mario Bauer, Matthias Bieg, Zuguang Gu, Dieter Weichenhan, Jan-Philipp Mallm, Stefan Röder, Gunda Herberth, Eiko Takada, Oliver Mücke, Marcus Winter, Kristin M Junge, Konrad Grützmann, Ulrike Rolle-Kampczyk, Qi Wang, Christian Lawerenz, Michael Borte, Tobias Polte, Matthias Schlesner, Michaela Schanne, Stefan Wiemann, Christina Geörg, Hendrik G Stunnenberg, Christoph Plass, Karsten Rippe, Junichiro Mizuguchi, Carl Herrmann, Roland Eils & Irina Lehmann |
| Summary: | 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. |
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| Item Description: | Gesehen am 27.02.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1744-4292 |
| DOI: | 10.15252/msb.20156520 |