TY  - JOUR
A1  - Witt, Stephanie H.
A1  - Frank, Josef
A1  - Gilles, Maria
A1  - Lang, Maren
A1  - Treutlein, Jens
A1  - Streit, Fabian
A1  - Wolf, Isabell A. C.
A1  - Peus, Verena
A1  - Scharnholz, Barbara
A1  - Send, Tabea S.
A1  - Heilmann-Heimbach, Stefanie
A1  - Sivalingam, Sugirthan
A1  - Dukal, Helene
A1  - Strohmaier, Jana
A1  - Sütterlin, Marc
A1  - Arloth, Janine
A1  - Laucht, Manfred
A1  - Nöthen, Markus M.
A1  - Deuschle, Michael
A1  - Rietschel, Marcella
T1  - Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation
JF  - BMC genomics
N2  - Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.
KW  - DNA methylation
KW  - Smoking
KW  - Birth weight
KW  - Mediation analysis
Y1  - 2018
U6  - https://doi.org/10.1186/s12864-018-4652-7
SN  - 1471-2164
VL  - 19
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Weyrich, Alexandra
A1  - Yasar, Selma
A1  - Lenz, Dorina
A1  - Fickel, Jörns
T1  - Tissue-specific epigenetic inheritance after paternal heat exposure in male wild guinea pigs
JF  - Mammalian genome
N2  - External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic responses. Here, we aim to address differential epigenetic responses on a gene and gene pathway level in two organs, liver and testis. We chose these organs, because the liver is the main metabolic and thermoregulation organ, and epigenetic modifications in testis are potentially transmitted to the F2 generation. We focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to an ambient temperature increase of 10 degrees C, and investigated differential methylated regions of sons sired before and after the paternal exposure using Reduced Representation Bisulfite Sequencing. We detected both a highly tissue-specific epigenetic response, reflected in genes involved in organ-specific metabolic pathways, and a more general regulation of single genes epigenetically modified in both organs. We conclude that genomes are context-specifically differentially epigenetically regulated in response to temperature increase. These findings emphasize the epigenetic relevance in cell differentiation, which is essential for the specific function(s) of complex organs, and is represented in a diverse molecular regulation of genes and gene pathways. The results also emphasize the paternal contribution to adaptive processes.
KW  - DNA methylation
KW  - gene-expression
KW  - CPG Islands
KW  - stress
KW  - hyperthermia
KW  - testis
Y1  - 2020
U6  - https://doi.org/10.1007/s00335-020-09832-6
SN  - 0938-8990
SN  - 1432-1777
VL  - 31
IS  - 5-6
SP  - 157
EP  - 169
PB  - Springer
CY  - New York
ER  - 
TY  - GEN
A1  - Weyrich, Alexandra
A1  - Yasar, Selma
A1  - Lenz, Dorina
A1  - Fickel, Jörns
T1  - Tissue-specific epigenetic inheritance after paternal heat exposure in male wild guinea pigs
T2  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic responses. Here, we aim to address differential epigenetic responses on a gene and gene pathway level in two organs, liver and testis. We chose these organs, because the liver is the main metabolic and thermoregulation organ, and epigenetic modifications in testis are potentially transmitted to the F2 generation. We focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to an ambient temperature increase of 10 degrees C, and investigated differential methylated regions of sons sired before and after the paternal exposure using Reduced Representation Bisulfite Sequencing. We detected both a highly tissue-specific epigenetic response, reflected in genes involved in organ-specific metabolic pathways, and a more general regulation of single genes epigenetically modified in both organs. We conclude that genomes are context-specifically differentially epigenetically regulated in response to temperature increase. These findings emphasize the epigenetic relevance in cell differentiation, which is essential for the specific function(s) of complex organs, and is represented in a diverse molecular regulation of genes and gene pathways. The results also emphasize the paternal contribution to adaptive processes.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1431 
KW  - DNA methylation
KW  - gene-expression
KW  - CPG Islands
KW  - stress
KW  - hyperthermia
KW  - testis
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-516525
SN  - 1866-8372
IS  - 5-6
ER  - 
TY  - JOUR
A1  - Weyrich, Alexandra
A1  - Lenz, Dorina
A1  - Jeschek, Marie
A1  - Tzu Hung Chung, 
A1  - Ruebensam, Kathrin
A1  - Goeritz, Frank
A1  - Jewgenow, Katarina
A1  - Fickel, Jörns
T1  - Paternal intergenerational epigenetic response to heat exposure in male Wild guinea pigs
JF  - Molecular ecology
N2  - Epigenetic modifications, of which DNA methylation is the best studied one, can convey environmental information through generations via parental germ lines. Past studies have focused on the maternal transmission of epigenetic information to the offspring of isogenic mice and rats in response to external changes, whereas heterogeneous wild mammals as well as paternal epigenetic effects have been widely neglected. In most wild mammal species, males are the dispersing sex and have to cope with differing habitats and thermal changes. As temperature is a major environmental factor we investigated if genetically heterogeneous Wild guinea pig (Cavia aperea) males can adapt epigenetically to an increase in temperature and if that response will be transmitted to the next generation(s). Five adult male guinea pigs (F0) were exposed to an increased ambient temperature for 2 months, i.e. the duration of spermatogenesis. We studied the liver (as the main thermoregulatory organ) of F0 fathers and F1 sons, and testes of F1 sons for paternal transmission of epigenetic modifications across generation(s). Reduced representation bisulphite sequencing revealed shared differentially methylated regions in annotated areas between F0 livers before and after heat treatment, and their sons’ livers and testes, which indicated a general response with ecological relevance. Thus, paternal exposure to a temporally limited increased ambient temperature led to an ‘immediate’ and ‘heritable’ epigenetic response that may even be transmitted to the F2 generation. In the context of globally rising temperatures epigenetic mechanisms may become increasingly relevant for the survival of species.
KW  - adaptation
KW  - Cavia aperea
KW  - DNA methylation
KW  - environmental factor
KW  - global change
KW  - plasticity
KW  - temperature increase
Y1  - 2016
U6  - https://doi.org/10.1111/mec.13494
SN  - 0962-1083
SN  - 1365-294X
VL  - 25
SP  - 1729
EP  - 1740
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Weyrich, Alexandra
A1  - Lenz, Dorina
A1  - Fickel, Jörns
T1  - Environmental Change-Dependent Inherited Epigenetic Response
JF  - GENES
N2  - Epigenetic modifications are a mechanism conveying environmental information to subsequent generations via parental germ lines. Research on epigenetic responses to environmental changes in wild mammals has been widely neglected, as well as studies that compare responses to changes in different environmental factors. Here, we focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to either diet (~40% less protein) or temperature increase (10 °C increased temperature). Because both experiments focused on the liver as the main metabolic and thermoregulation organ, we were able to decipher if epigenetic changes differed in response to different environmental changes. Reduced representation bisulfite sequencing (RRBS) revealed differentially methylated regions (DMRs) in annotated genomic regions in sons sired before (control) and after the fathers’ treatments. We detected both a highly specific epigenetic response dependent on the environmental factor that had changed that was reflected in genes involved in specific metabolic pathways, and a more general response to changes in outer stimuli reflected by epigenetic modifications in a small subset of genes shared between both responses. Our results indicated that fathers prepared their offspring for specific environmental changes by paternally inherited epigenetic modifications, suggesting a strong paternal contribution to adaptive processes.
KW  - DNA methylation
KW  - exposure
KW  - wild mammal species
KW  - inheritance
KW  - plasticity
KW  - adaptation
KW  - RRBS
Y1  - 2018
U6  - https://doi.org/10.3390/genes10010004
SN  - 2073-4425
VL  - 10
IS  - 1
PB  - MDPI
CY  - Basel
ER  - 
TY  - GEN
A1  - Weyrich, Alexandra
A1  - Jeschek, Marie
A1  - Schrapers, Katharina T.
A1  - Lenz, Dorina
A1  - Chung, Tzu Hung
A1  - Ruebensam, Kathrin
A1  - Yasar, Sermin
A1  - Schneemann, Markus
A1  - Ortmann, Sylvia
A1  - Jewgenow, Katarina
A1  - Fickel, Jörns
T1  - Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring's adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father's LPD treatment in both, liver and testis tissues. Our results point to a 'heritable epigenetic response' of the sons to the fathers' dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming ('metabolic shift'). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1065 
KW  - DNA methylation
KW  - exposure
KW  - wild mammal species
KW  - inheritance
KW  - plasticity
KW  - adaptation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-460031
SN  - 1866-8372
IS  - 1065
ER  - 
TY  - JOUR
A1  - Weyrich, Alexandra
A1  - Jeschek, Marie
A1  - Schrapers, Katharina T.
A1  - Lenz, Dorina
A1  - Chung, Tzu Hung
A1  - Ruebensam, Kathrin
A1  - Yasar, Sermin
A1  - Schneemann, Markus
A1  - Ortmann, Sylvia
A1  - Jewgenow, Katarina
A1  - Fickel, Jörns
T1  - Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs
JF  - Environmental Epigenetics
N2  - Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring’s adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father’s LPD treatment in both, liver and testis tissues. Our results point to a ‘heritable epigenetic response’ of the sons to the fathers’ dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming (‘metabolic shift’). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.
KW  - DNA methylation
KW  - exposure
KW  - wild mammal species
KW  - inheritance
KW  - plasticity
KW  - adaptation
Y1  - 2018
U6  - https://doi.org/10.1093/eep/dvy011
SN  - 2058-5888
VL  - 4
IS  - 2
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Weyrich, Alexandra
A1  - Benz, Stephanie
A1  - Karl, Stephan
A1  - Jeschek, Marie
A1  - Jewgenow, Katarina
A1  - Fickel, Jörns
T1  - Paternal heat exposure causes DNA methylation and gene expression changes of Stat3 in Wild guinea pig sons
JF  - Ecology and evolution
N2  - Epigenetic mechanisms convey environmental information through generations and can regulate gene expression. Epigenetic studies in wild mammals are rare, but enable understanding adaptation processes as they may occur in nature. In most wild mammal species, males are the dispersing sex and thus often have to cope with differing habitats and thermal changes more rapidly than the often philopatric females. As temperature is a major environmental selection factor, we investigated whether genetically heterogeneous Wild guinea pig (Cavia aperea) males adapt epigenetically to an increase in temperature, whether that response will be transmitted to the next generation(s), and whether it regulates mRNA expression. Five (F0) adult male guinea pigs were exposed to an increased ambient temperature for 2 months, corresponding to the duration of the species' spermatogenesis. To study the effect of heat, we focused on the main thermoregulatory organ, the liver. We analyzed CpG-methylation changes of male offspring (F1) sired before and after the fathers' heat treatment (as has recently been described in Weyrich et al. [Mol. Ecol., 2015]). Transcription analysis was performed for the three genes with the highest number of differentially methylated changes detected: the thermoregulation gene Signal Transducer and Activator of Transcription 3 (Stat3), the proteolytic peptidase gene Cathepsin Z (Ctsz), and Sirtuin 6 (Sirt6) with function in epigenetic regulation. Stat3 gene expression was significantly reduced (P < 0.05), which indicated a close link between CpG-methylation and expression levels for this gene. The two other genes did not show gene expression changes. Our results indicate the presence of a paternal transgenerational epigenetic effect. Quick adaptation to climatic changes may become increasingly relevant for the survival of wildlife species as global temperatures are rising.
KW  - Adaptation
KW  - DNA methylation
KW  - nonmodel species
KW  - Paternal effects
KW  - thermoregulation
KW  - transgenerational epigenetic inheritance
Y1  - 2016
U6  - https://doi.org/10.1002/ece3.1993
SN  - 2045-7758
VL  - 6
SP  - 2657
EP  - 2666
PB  - Wiley
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - von Websky, Karoline
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Reichetzeder, Christoph
A1  - Tsuprykov, Oleg
A1  - Hocher, Berthold
T1  - Impact of vitamin D on pregnancy-related disorders and on offspring outcome
JF  - The Journal of Steroid Biochemistry and Molecular Biology
N2  - Observational studies from all over the world continue to find high prevalence rates of vitamin D insufficiency and deficiency in many populations, including pregnant women. Beyond its classical function as a regulator of calcium and phosphate metabolism, vitamin D elicits numerous effects in the human body. Current evidence highlights a vital role of vitamin D in mammalian gestation. During pregnancy, adaptations in maternal vitamin D metabolism lead to a physiologic increase of vitamin D levels, mainly because of an increased renal production, although other potential sources like the placenta are being discussed. A sufficient supply of mother and child with calcium and vitamin D during pregnancy ensures a healthy bone development of the fetus, whereas lack of either of these nutrients can lead to the development of rickets in the child. Moreover, vitamin D insufficiency during pregnancy has consistently been associated with adverse maternal and neonatal pregnancy outcomes. In multitudinous studies, low maternal vitamin D status was associated with a higher risk for pre-eclampsia, gestational diabetes mellitus and other gestational diseases. Likewise, several negative consequences for the fetus have been reported, including fetal growth restriction, increased risk of preterm birth and a changed susceptibility for later-life diseases. However, study results are diverging and causality has not been proven so far. Meta-analyses on the relationship between maternal vitamin D status and pregnancy outcomes revealed a wide heterogeneity of studied populations and the applied methodology in vitamin D assessment. Until today, clinical guidelines for supplementation cannot be based on high-quality evidence and it is not clear if the required intake for pregnant women differs from non-pregnant women. Long-term safety data of vitamin D supplementation in pregnant women has not been established and overdosing of vitamin D might have unfavorable effects, especially in mothers and newborns with mutations of genes involved in vitamin D metabolism. Reliable data from large observational and interventional randomized control trials are urgently needed as a basis for any detailed and safe recommendations for supplementation in the general population and, most importantly, in pregnant women. This is of utmost importance, as ensuring a sufficient vitamin D-supply of mother and child implies a great potential for the prevention of birth complications and development of diseases.
KW  - Vitamin D deficiency
KW  - Free vitamin D
KW  - Vitamin D binding protein
KW  - Epigenetics
KW  - DNA methylation
KW  - Single nucleotide polymorphism
KW  - Preeclampsia
KW  - Gestational diabetes mellitus
KW  - Small for gestational age
KW  - Long term health
Y1  - 2018
U6  - https://doi.org/10.1016/j.jsbmb.2017.11.008
SN  - 0960-0760
VL  - 180
SP  - 51
EP  - 64
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - GEN
A1  - Teif, Vladimir B.
A1  - Cherstvy, Andrey G.
T1  - Chromatin and epigenetics: current biophysical views
T2  - AIMS biophysics
N2  - Recent advances in high-throughput sequencing experiments and their theoretical descriptions have determined fast dynamics of the "chromatin and epigenetics" field, with new concepts appearing at high rate. This field includes but is not limited to the study of DNA-protein-RNA interactions, chromatin packing properties at different scales, regulation of gene expression and protein trafficking in the cell nucleus, binding site search in the crowded chromatin environment and modulation of physical interactions by covalent chemical modifications of the binding partners. The current special issue does not pretend for the full coverage of the field, but it rather aims to capture its development and provide a snapshot of the most recent concepts and approaches. Eighteen open-access articles comprising this issue provide a delicate balance between current theoretical and experimental biophysical approaches to uncover chromatin structure and understand epigenetic regulation, allowing free flow of new ideas and preliminary results.
KW  - chromatin
KW  - epigenetics
KW  - linker histones
KW  - nucleosome
KW  - DNA-protein binding
KW  - histone modifications
KW  - remodelers
KW  - topologically associated domains
KW  - DNA methylation
KW  - DNA supercoiling
Y1  - 2016
U6  - https://doi.org/10.3934/biophy.2016.1.88
SN  - 2377-9098
VL  - 3
SP  - 88
EP  - 98
PB  - American Institute of Mathematical Sciences
CY  - Springfield
ER  -