TY  - JOUR
A1  - Guerrero, Tania P.
A1  - Fickel, Jörns
A1  - Benhaiem, Sarah
A1  - Weyrich, Alexandra
T1  - Epigenomics and gene regulation in mammalian social systems
JF  - Current zoology
N2  - Social epigenomics is a new field of research that studies how the social environment shapes the epigenome and how in turn the epigenome modulates behavior. We focus on describing known gene-environment interactions (GEIs) and epigenetic mechanisms in different mammalian social systems. To illustrate how epigenetic mechanisms integrate GEls, we highlight examples where epigenetic mechanisms are associated with social behaviors and with their maintenance through neuroendocrine, locomotor, and metabolic responses. We discuss future research trajectories and open questions for the emerging field of social epigenomics in nonmodel and naturally occurring social systems. Finally, we outline the technological advances that aid the study of epigenetic mechanisms in the establishment of GEIs and vice versa.
KW  - epigenetics
KW  - DNA methylation
KW  - histone modification
KW  - rank
KW  - social status
KW  - social systems
Y1  - 2020
U6  - https://doi.org/10.1093/cz/zoaa005
SN  - 1674-5507
SN  - 2396-9814
VL  - 66
IS  - 3
SP  - 307
EP  - 319
PB  - Oxford Univ. Press
CY  - Oxford
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  - JOUR
A1  - Saussenthaler, Sophie
A1  - Ouni, Meriem
A1  - Baumeier, Christian
A1  - Schwerbel, Kristin
A1  - Gottmann, Pascal
A1  - Christmann, Sabrina
A1  - Laeger, Thomas
A1  - Schürmann, Annette
T1  - Epigenetic regulation of hepatic Dpp4 expression in response to dietary protein
JF  - The journal of nutritional biochemistry
N2  - Dipeptidyl peptidase 4 (DPP4) is known to be elevated in metabolic disturbances such as obesity, type 2 diabetes and fatty liver disease. Lowering DPP4 concentration by pharmacological inhibition improves glucose homeostasis and exhibits beneficial effects to reduce hepatic fat content. As factors regulating the endogenous expression of Dpp4 are unknown, the aim of this study was to examine whether the Dpp4 expression is epigenetically regulated in response to dietary components. Primary hepatocytes were treated with different macronutrients, and Dpp4 mRNA levels and DPP4 activity were evaluated. Moreover, dietary low-protein intervention was conducted in New Zealand obese (NZO) mice, and subsequently, effects on Dpp4 expression, methylation as well as plasma concentration and activity were determined. Our results indicate that Dpp4 mRNA expression is mediated by DNA methylation in several tissues. We therefore consider the Dpp4 southern shore as tissue differentially methylated region. Amino acids increased Dpp4 expression in primary hepatocytes, whereas glucose and fatty acids were without effect. Dietary protein restriction in NZO mice increased Dpp4 DNA methylation in liver leading to diminished Dpp4 expression and consequently to lowered plasma DPP4 activity. We conclude that protein restriction in the adolescent and adult states is a sufficient strategy to reduce DPP4 which in turn contributes to improve glucose homeostasis. (C) 2018 Published by Elsevier Inc.
KW  - DPP4
KW  - DNA methylation
KW  - Protein restriction
KW  - Type 2 diabetes
KW  - NZO
Y1  - 2019
U6  - https://doi.org/10.1016/j.jnutbio.2018.09.025
SN  - 0955-2863
SN  - 1873-4847
VL  - 63
SP  - 109
EP  - 116
PB  - Elsevier
CY  - New York
ER  - 
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  - 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  - 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  - 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  - Lämke, Jörn
A1  - Bäurle, Isabel
T1  - Epigenetic and chromatin-based mechanisms in environmental stress adaptation and stress memory in plants
JF  - Genome biology : biology for the post-genomic era
N2  - Plants frequently have to weather both biotic and abiotic stressors, and have evolved sophisticated adaptation and defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, and DNA methylation have been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for a stress memory, enabling plants to respond more efficiently to recurring stress or even to prepare their offspring for potential future assaults. In this review, we discuss both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory.
KW  - remodeling atpase brahma
KW  - transcriptional memory
KW  - DNA methylation
KW  - transgenerational inheritance
KW  - acquired thermotolerance
KW  - Arabidopsis-thaliana
KW  - gene-expression
KW  - responses
KW  - protein
KW  - defense
Y1  - 2017
U6  - https://doi.org/10.1186/s13059-017-1263-6
SN  - 1474-760X
VL  - 18
SP  - 8685
EP  - 8693
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Putra, Sulistyo E. Dwi
A1  - Reichetzeder, Christoph
A1  - Meixner, Martin
A1  - Liere, Karsten
A1  - Slowinski, Torsten
A1  - Hocher, Berthold
T1  - DNA methylation of the glucocorticoid receptor gene promoter in the placenta is associated with blood pressure regulation in human pregnancy
JF  - Journal of hypertension
N2  - Background: Blood pressure (BP) regulation during pregnancy is influenced by hormones of placental origin. It was shown that the glucocorticoid system is altered in hypertensive pregnancy disorders such as preeclampsia. Epigenetic mechanism might influence the activity of genes involved in placental hormone/hormone receptor synthesis/action during pregnancy. Method: In the current study, we analyzed the association of 50-C-phosphate-G-30 (CpG) site methylation of different glucocorticoid receptor gene (NR3C1) promoter regions with BP during pregnancy. The study was performed as a nested case-control study (n = 80) out of 1045 mother/ child pairs from the Berlin Birth Cohort. Placental DNA was extracted and bisulfite converted. Nested PCR products from six NR3C1 proximal promoter regions [glucocorticoid receptor gene promotor region B (GR-1B), C (GR-1C), D (GR-1D), E (GR-1E), F (GR-1F), and H (GR-1H)] were analyzed by next generation sequencing. Results: NR3C1 promoter regions GR-1D and GR-1E had a much higher degree of DNA methylation as compared to GR-1B, GR-1F or GR-1H when analyzing the entire study population. Comparison of placental NR3C1 CpG site methylation among hypotensive, normotensive and hypertensive mothers revealed several differently methylated CpG sites in the GR-1F promoter region only. Both hypertension and hypotension were associated with increased DNA methylation of GR-1F CpG sites. These associations were independent of confounding factors, such as family history of hypertension, smoking status before pregnancy and prepregnancy BMI. Assessment of placental glucocorticoid receptor expression by western blot showed that observed DNA methylation differences were not associated with altered levels of placental glucocorticoid receptor expression. However, correlation matrices of all NR3C1 proximal promoter regions demonstrated different correlation patterns of intraregional and interregional DNA methylation in the three BP groups, putatively indicating altered transcriptional control of glucocorticoid receptor isoforms. Conclusion: Our study provides evidence of an independent association between placental NR3C1 proximal promoter methylation and maternal BP. Furthermore, we observed different patterns of NR3C1 promoter methylation in normotensive, hypertensive and hypotensive pregnancy.
KW  - DNA methylation
KW  - epigenetics
KW  - glucocorticoid receptor
KW  - hypertension
KW  - hypotension
KW  - NR3C1 gene
KW  - placenta
KW  - pregnancy
Y1  - 2017
U6  - https://doi.org/10.1097/HJH.0000000000001450
SN  - 0263-6352
SN  - 1473-5598
VL  - 35
SP  - 2276
EP  - 2286
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Speckmann, Bodo
A1  - Schulz, Sarah
A1  - Hiller, Franziska
A1  - Hesse, Deike
A1  - Schumacher, Fabian
A1  - Kleuser, Burkhard
A1  - Geisel, Juergen
A1  - Obeid, Rima
A1  - Grune, Tilman
A1  - Kipp, Anna Patricia
T1  - Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice
JF  - The journal of nutritional biochemistry
N2  - The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc.
KW  - Selenium
KW  - DNA methylation
KW  - Liver
KW  - Lipogenesis
KW  - Srebf1
Y1  - 2017
U6  - https://doi.org/10.1016/j.jnutbio.2017.07.002
SN  - 0955-2863
SN  - 1873-4847
VL  - 48
SP  - 112
EP  - 119
PB  - Elsevier
CY  - New York
ER  -