TY - JOUR A1 - Kanzleiter, Timo A1 - Jaehnert, Markus A1 - Schulze, Gunnar A1 - Selbig, Joachim A1 - Hallahan, Nicole A1 - Schwenk, Robert Wolfgang A1 - Schürmann, Annette T1 - Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in mice JF - American journal of physiology : Endocrinology and metabolism N2 - The adaptive response of skeletal muscle to exercise training is tightly controlled and therefore requires transcriptional regulation. DNA methylation is an epigenetic mechanism known to modulate gene expression, but its contribution to exercise-induced adaptations in skeletal muscle is not well studied. Here, we describe a genome-wide analysis of DNA methylation in muscle of trained mice (n = 3). Compared with sedentary controls, 2,762 genes exhibited differentially methylated CpGs (P < 0.05, meth diff >5%, coverage > 10) in their putative promoter regions. Alignment with gene expression data (n = 6) revealed 200 genes with a negative correlation between methylation and expression changes in response to exercise training. The majority of these genes were related to muscle growth and differentiation, and a minor fraction involved in metabolic regulation. Among the candidates were genes that regulate the expression of myogenic regulatory factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motor neuron innervation (Dok7). Interestingly, a transcription factor binding site enrichment study discovered significantly enriched occurrence of CpG methylation in the binding sites of the myogenic regulatory factors MyoD and myogenin. These findings suggest that DNA methylation is involved in the regulation of muscle adaptation to regular exercise training. KW - DNA methylation KW - regular exercise training KW - muscle development Y1 - 2015 U6 - https://doi.org/10.1152/ajpendo.00289.2014 SN - 0193-1849 SN - 1522-1555 VL - 308 IS - 10 SP - E912 EP - E920 PB - American Chemical Society CY - Bethesda 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 - 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 - 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 - 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 - 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 - 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 -