@article{BerryRosaHowardetal.2017, author = {Berry, Scott and Rosa, Stefanie and Howard, Martin and Buhler, Marc and Dean, Caroline}, title = {Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression}, series = {Genes \& Development}, volume = {31}, journal = {Genes \& Development}, publisher = {Cold Spring Harbor Laboratory Press}, address = {Cold Spring Harbor, NY}, issn = {0890-9369}, doi = {10.1101/gad.305227.117}, pages = {2115 -- 2120}, year = {2017}, abstract = {Epigenetic maintenance of gene repression is essential for development. Polycomb complexes are central to this memory, but many aspects of the underlying mechanism remain unclear. LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binds Polycomb-deposited H3K27me3 and is required for repression of many Polycomb target genes in Arabidopsis. Here we show that LHP1 binds RNA in vitro through the intrinsically disordered hinge region. By independently perturbing the RNA-binding hinge region and H3K27me3 (trimethylation of histone H3 at Lys27) recognition, we found that both facilitate LHP1 localization and H3K27me3 maintenance. Disruption of the RNAbinding hinge region also prevented formation of subnuclear foci, structures potentially important for epigenetic repression.}, language = {en} } @phdthesis{Eckert2022, author = {Eckert, Silvia}, title = {Trait variation in changing environments: Assessing the role of DNA methylation in non-native plant species}, doi = {10.25932/publishup-56884}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-568844}, school = {Universit{\"a}t Potsdam}, pages = {VIII, 134, CXXX}, year = {2022}, abstract = {The increasing introduction of non-native plant species may pose a threat to local biodiversity. However, the basis of successful plant invasion is not conclusively understood, especially since these plant species can adapt to the new range within a short period of time despite impoverished genetic diversity of the starting populations. In this context, DNA methylation is considered promising to explain successful adaptation mechanisms in the new habitat. DNA methylation is a heritable variation in gene expression without changing the underlying genetic information. Thus, DNA methylation is considered a so-called epigenetic mechanism, but has been studied in mainly clonally reproducing plant species or genetic model plants. An understanding of this epigenetic mechanism in the context of non-native, predominantly sexually reproducing plant species might help to expand knowledge in biodiversity research on the interaction between plants and their habitats and, based on this, may enable more precise measures in conservation biology. For my studies, I combined chemical DNA demethylation of field-collected seed material from predominantly sexually reproducing species and rearing offsping under common climatic conditions to examine DNA methylation in an ecological-evolutionary context. The contrast of chemically treated (demethylated) plants, whose variation in DNA methylation was artificially reduced, and untreated control plants of the same species allowed me to study the impact of this mechanism on adaptive trait differentiation and local adaptation. With this experimental background, I conducted three studies examining the effect of DNA methylation in non-native species along a climatic gradient and also between climatically divergent regions. The first study focused on adaptive trait differentiation in two invasive perennial goldenrod species, Solidago canadensis sensu latu and S. gigantea AITON, along a climate gradient of more than 1000 km in length in Central Europe. I found population differences in flowering timing, plant height, and biomass in the temporally longer-established S. canadensis, but only in the number of regrowing shoots for S. gigantea. While S. canadensis did not show any population structure, I was able to identify three genetic groups along this climatic gradient in S. gigantea. Surprisingly, demethylated plants of both species showed no change in the majority of traits studied. In the subsequent second study, I focused on the longer-established goldenrod species S. canadensis and used molecular analyses to infer spatial epigenetic and genetic population differences in the same specimens from the previous study. I found weak genetic but no epigenetic spatial variation between populations. Additionally, I was able to identify one genetic marker and one epigenetic marker putatively susceptible to selection. However, the results of this study reconfirmed that the epigenetic mechanism of DNA methylation appears to be hardly involved in adaptive processes within the new range in S. canadensis. Finally, I conducted a third study in which I reciprocally transplanted short-lived plant species between two climatically divergent regions in Germany to investigate local adaptation at the plant family level. For this purpose, I used four plant families (Amaranthaceae, Asteraceae, Plantaginaceae, Solanaceae) and here I additionally compared between non-native and native plant species. Seeds were transplanted to regions with a distance of more than 600 kilometers and had either a temperate-oceanic or a temperate-continental climate. In this study, some species were found to be maladapted to their own local conditions, both in non-native and native plant species alike. In demethylated individuals of the plant species studied, DNA methylation had inconsistent but species-specific effects on survival and biomass production. The results of this study highlight that DNA methylation did not make a substantial contribution to local adaptation in the non-native as well as native species studied. In summary, my work showed that DNA methylation plays a negligible role in both adaptive trait variation along climatic gradients and local adaptation in non-native plant species that either exhibit a high degree of genetic variation or rely mainly on sexual reproduction with low clonal propagation. I was able to show that the adaptive success of these non-native plant species can hardly be explained by DNA methylation, but could be a possible consequence of multiple introductions, dispersal corridors and meta-population dynamics. Similarly, my results illustrate that the use of plant species that do not predominantly reproduce clonally and are not model plants is essential to characterize the effect size of epigenetic mechanisms in an ecological-evolutionary context.}, language = {en} } @misc{FriedrichFaivreBaeurleetal.2018, author = {Friedrich, Thomas and Faivre, Lea and B{\"a}urle, Isabel and Schubert, Daniel}, title = {Chromatin-based mechanisms of temperature memory in plants}, series = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology}, volume = {42}, journal = {Plant, cell \& environment : cell physiology, whole-plant physiology, community physiology}, number = {3}, publisher = {Wiley}, address = {Hoboken}, issn = {0140-7791}, doi = {10.1111/pce.13373}, pages = {762 -- 770}, year = {2018}, abstract = {For successful growth and development, plants constantly have to gauge their environment. Plants are capable to monitor their current environmental conditions, and they are also able to integrate environmental conditions over time and store the information induced by the cues. In a developmental context, such an environmental memory is used to align developmental transitions with favourable environmental conditions. One temperature-related example of this is the transition to flowering after experiencing winter conditions, that is, vernalization. In the context of adaptation to stress, such an environmental memory is used to improve stress adaptation even when the stress cues are intermittent. A somatic stress memory has now been described for various stresses, including extreme temperatures, drought, and pathogen infection. At the molecular level, such a memory of the environment is often mediated by epigenetic and chromatin modifications. Histone modifications in particular play an important role. In this review, we will discuss and compare different types of temperature memory and the histone modifications, as well as the reader, writer, and eraser proteins involved.}, language = {en} } @article{GereckeSchumacherBerndzenetal.2019, author = {Gerecke, Christian and Schumacher, Fabian and Berndzen, Alide and Homann, Thomas and Kleuser, Burkhard}, title = {Vitamin C in combination with inhibition of mutant IDH1 synergistically activates TET enzymes and epigenetically modulates gene silencing in colon cancer cells}, series = {Epigenetics : the official journal of the DNA Methylation Society}, volume = {15}, journal = {Epigenetics : the official journal of the DNA Methylation Society}, number = {3}, publisher = {Taylor \& Francis Group}, address = {Philadelphia}, issn = {1559-2294}, doi = {10.1080/15592294.2019.1666652}, pages = {307 -- 322}, year = {2019}, abstract = {Mutations in the enzyme isocitrate dehydrogenase 1 (IDH1) lead to metabolic alterations and a sustained formation of 2-hydroxyglutarate (2-HG). 2-HG is an oncometabolite as it inhibits the activity of alpha-ketoglutarate-dependent dioxygenases such as ten-eleven translocation (TET) enzymes. Inhibitors of mutant IDH enzymes, like ML309, are currently tested in order to lower the levels of 2-HG. Vitamin C (VC) is an inducer of TET enzymes. To test a new therapeutic avenue of synergistic effects, the anti-neoplastic activity of inhibition of mutant IDH1 via ML309 in the presence of VC was investigated in the colon cancer cell line HCT116 IDH1(R132H/+) (harbouring a mutated IDH1 allele) and the parental cells HCT116 IDH1(+/+) (wild type IDH1). Measurement of the oncometabolite indicated a 56-fold higher content of 2-HG in mutated cells compared to wild type cells. A significant reduction of 2-HG was observed in mutated cells after treatment with ML 309, whereas VC produced only minimally changes of the oncometabolite. However, combinatorial treatment with both, ML309 and VC, in mutated cells induced pronounced reduction of 2-HG leading to levels comparable to those in wild type cells. The decreased level of 2-HG in mutated cells after combinatorial treatment was accompanied by an enhanced global DNA hydroxymethylation and an increased gene expression of certain tumour suppressors. Moreover, mutated cells showed an increased percentage of apoptotic cells after treatment with non-cytotoxic concentrations of ML309 and VC. These results suggest that combinatorial therapy is of interest for further investigation to rescue TET activity and treatment of IDH1/2 mutated cancers.}, language = {en} } @article{GuerreroFickelBenhaiemetal.2020, author = {Guerrero, Tania P. and Fickel, J{\"o}rns and Benhaiem, Sarah and Weyrich, Alexandra}, title = {Epigenomics and gene regulation in mammalian social systems}, series = {Current zoology}, volume = {66}, journal = {Current zoology}, number = {3}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {1674-5507}, doi = {10.1093/cz/zoaa005}, pages = {307 -- 319}, year = {2020}, abstract = {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.}, language = {en} } @article{HerdenEckertStiftetal.2019, author = {Herden, Jasmin and Eckert, Silvia and Stift, Marc and Joshi, Jasmin Radha and van Kleunen, Mark}, title = {No evidence for local adaptation and an epigenetic underpinning in native and non-native ruderal plant species in Germany}, series = {Ecology and evolution}, volume = {9}, journal = {Ecology and evolution}, number = {17}, publisher = {Wiley}, address = {Hoboken}, issn = {2045-7758}, doi = {10.1002/ece3.5325}, pages = {9412 -- 9426}, year = {2019}, abstract = {Many invasive species have rapidly adapted to different environments in their new ranges. This is surprising, as colonization is usually associated with reduced genetic variation. Heritable phenotypic variation with an epigenetic basis may explain this paradox. Here, we assessed the contribution of DNA methylation to local adaptation in native and naturalized non-native ruderal plant species in Germany. We reciprocally transplanted offspring from natural populations of seven native and five non-native plant species between the Konstanz region in the south and the Potsdam region in the north of Germany. Before the transplant, half of the seeds were treated with the demethylation agent zebularine. We recorded survival, flowering probability, and biomass production as fitness estimates. Contrary to our expectations, we found little evidence for local adaptation, both among the native and among the non-native plant species. Zebularine treatment had mostly negative effects on overall plant performance, regardless of whether plants were local or not, and regardless of whether they were native or non-native. Synthesis. We conclude that local adaptation, at least at the scale of our study, plays no major role in the success of non-native and native ruderal plants. Consequently, we found no evidence yet for an epigenetic basis of local adaptation.}, language = {en} } @article{HilkerSchwachtjeBaieretal.2016, author = {Hilker, Monika and Schwachtje, Jens and Baier, Margarete and Balazadeh, Salma and B{\"a}urle, Isabel and Geiselhardt, Sven and Hincha, Dirk K. and Kunze, Reinhard and Mueller-Roeber, Bernd and Rillig, Matthias G. and Rolff, Jens and Schm{\"u}lling, Thomas and Steppuhn, Anke and van Dongen, Joost and Whitcomb, Sarah J. and Wurst, Susanne and Zuther, Ellen and Kopka, Joachim}, title = {Priming and memory of stress responses in organisms lacking a nervous system}, series = {Biological reviews}, volume = {91}, journal = {Biological reviews}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1464-7931}, doi = {10.1111/brv.12215}, pages = {1118 -- 1133}, year = {2016}, language = {en} } @article{JonasSchuermann2020, author = {Jonas, Wenke and Sch{\"u}rmann, Annette}, title = {Genetic and epigenetic factors determining NAFLD risk}, series = {Molecular metabolism}, volume = {50}, journal = {Molecular metabolism}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2212-8778}, doi = {10.1016/j.molmet.2020.101111}, pages = {14}, year = {2020}, abstract = {Background: Hepatic steatosis is a common chronic liver disease that can progress into more severe stages of NAFLD or promote the development of life-threatening secondary diseases for some of those affected. These include the liver itself (nonalcoholic steatohepatitis or NASH; fibrosis and cirrhosis, and hepatocellular carcinoma) or other organs such as the vessels and the heart (cardiovascular disease) or the islets of Langerhans (type 2 diabetes). In addition to elevated caloric intake and a sedentary lifestyle, genetic and epigenetic predisposition contribute to the development of NAFLD and the secondary diseases. Scope of review: We present data from genome-wide association studies (GWAS) and functional studies in rodents which describe polymorphisms identified in genes relevant for the disease as well as changes caused by altered DNA methylation and gene regulation via specific miRNAs. The review also provides information on the current status of the use of genetic and epigenetic factors as risk markers. Major conclusion: With our overview we provide an insight into the genetic and epigenetic landscape of NAFLD and argue about the applicability of currently defined risk scores for risk stratification and conclude that further efforts are needed to make the scores more usable and meaningful.}, language = {en} } @misc{LiTsuprykovYangetal.2016, author = {Li, Jian and Tsuprykov, Oleg and Yang, Xiaoping and Hocher, Berthold}, title = {Paternal programming of offspring cardiometabolic diseases in later life}, series = {Journal of hypertension}, volume = {34}, journal = {Journal of hypertension}, publisher = {Wiley-Blackwell}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0000000000001051}, pages = {2111 -- 2126}, year = {2016}, language = {en} } @article{LiuLaemkeLinetal.2018, author = {Liu, Hsiang-chin and L{\"a}mke, J{\"o}rn and Lin, Siou-ying and Hung, Meng-Ju and Liu, Kuan-Ming and Charng, Yee-yung and B{\"a}urle, Isabel}, title = {Distinct heat shock factors and chromatin modifications mediate the organ-autonomous transcriptional memory of heat stress}, series = {The plant journal}, volume = {95}, journal = {The plant journal}, number = {3}, publisher = {Wiley}, address = {Hoboken}, issn = {0960-7412}, doi = {10.1111/tpj.13958}, pages = {401 -- 413}, year = {2018}, abstract = {Plants can be primed by a stress cue to mount a faster or stronger activation of defense mechanisms upon subsequent stress. A crucial component of such stress priming is the modified reactivation of genes upon recurring stress; however, the underlying mechanisms of this are poorly understood. Here, we report that dozens of Arabidopsis thaliana genes display transcriptional memory, i.e. stronger upregulation after a recurring heat stress, that lasts for at least 3 days. We define a set of transcription factors involved in this memory response and show that the transcriptional memory results in enhanced transcriptional activation within minutes of the onset of a heat stress cue. Further, we show that the transcriptional memory is active in all tissues. It may last for up to a week, and is associated during this time with histone H3 lysine 4 hypermethylation. This transcriptional memory is cis-encoded, as we identify a promoter fragment that confers memory onto a heterologous gene. In summary, heat-induced transcriptional memory is a widespread and sustained response, and our study provides a framework for future mechanistic studies of somatic stress memory in higher plants.}, language = {en} }