TY - JOUR A1 - Hilker, Monika A1 - Schwachtje, Jens A1 - Baier, Margarete A1 - Balazadeh, Salma A1 - Bäurle, Isabel A1 - Geiselhardt, Sven A1 - Hincha, Dirk K. A1 - Kunze, Reinhard A1 - Mueller-Roeber, Bernd A1 - Rillig, Matthias G. A1 - Rolff, Jens A1 - Schmülling, Thomas A1 - Steppuhn, Anke A1 - van Dongen, Joost A1 - Whitcomb, Sarah J. A1 - Wurst, Susanne A1 - Zuther, Ellen A1 - Kopka, Joachim T1 - Priming and memory of stress responses in organisms lacking a nervous system JF - Biological reviews KW - priming KW - stress signalling KW - epigenetics KW - memory KW - fitness KW - stress tolerance KW - defence KW - bet hedging Y1 - 2016 U6 - https://doi.org/10.1111/brv.12215 SN - 1464-7931 SN - 1469-185X VL - 91 SP - 1118 EP - 1133 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Berry, Scott A1 - Rosa, Stefanie A1 - Howard, Martin A1 - Buhler, Marc A1 - Dean, Caroline T1 - Disruption of an RNA-binding hinge region abolishes LHP1-mediated epigenetic repression JF - Genes & Development N2 - 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. KW - chromatin KW - epigenetics KW - plant biology KW - Polycomb KW - RNA Y1 - 2017 U6 - https://doi.org/10.1101/gad.305227.117 SN - 0890-9369 SN - 1549-5477 VL - 31 SP - 2115 EP - 2120 PB - Cold Spring Harbor Laboratory Press CY - Cold Spring Harbor, NY 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 - Liu, Hsiang-chin A1 - Lämke, Jörn A1 - Lin, Siou-ying A1 - Hung, Meng-Ju A1 - Liu, Kuan-Ming A1 - Charng, Yee-yung A1 - Bäurle, Isabel T1 - Distinct heat shock factors and chromatin modifications mediate the organ-autonomous transcriptional memory of heat stress JF - The plant journal N2 - 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. KW - epigenetics KW - priming KW - heat stress KW - H3K4 methylation KW - transcriptional memory KW - Arabidopsis thaliana KW - HSF Y1 - 2018 U6 - https://doi.org/10.1111/tpj.13958 SN - 0960-7412 SN - 1365-313X VL - 95 IS - 3 SP - 401 EP - 413 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Gerecke, Christian A1 - Schumacher, Fabian A1 - Berndzen, Alide A1 - Homann, Thomas A1 - Kleuser, Burkhard T1 - Vitamin C in combination with inhibition of mutant IDH1 synergistically activates TET enzymes and epigenetically modulates gene silencing in colon cancer cells JF - Epigenetics : the official journal of the DNA Methylation Society N2 - 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. KW - Vitamin C KW - epigenetics KW - IDH1 KW - TET KW - cancer cells Y1 - 2019 U6 - https://doi.org/10.1080/15592294.2019.1666652 SN - 1559-2294 SN - 1559-2308 VL - 15 IS - 3 SP - 307 EP - 322 PB - Taylor & Francis Group CY - Philadelphia ER - TY - JOUR A1 - Herden, Jasmin A1 - Eckert, Silvia A1 - Stift, Marc A1 - Joshi, Jasmin Radha A1 - van Kleunen, Mark T1 - No evidence for local adaptation and an epigenetic underpinning in native and non-native ruderal plant species in Germany JF - Ecology and evolution N2 - 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. KW - biological invasions KW - epigenetics KW - local adaptation KW - reciprocal transplant experiment KW - ruderal plant species KW - zebularine Y1 - 2019 U6 - https://doi.org/10.1002/ece3.5325 SN - 2045-7758 VL - 9 IS - 17 SP - 9412 EP - 9426 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Jonas, Wenke A1 - Schürmann, Annette T1 - Genetic and epigenetic factors determining NAFLD risk JF - Molecular metabolism N2 - 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. KW - NAFLD KW - genetic variants KW - epigenetics KW - risk score Y1 - 2020 U6 - https://doi.org/10.1016/j.molmet.2020.101111 SN - 2212-8778 VL - 50 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Moreno-Romero, Jordi A1 - Probst, Aline V. A1 - Trindade, Inês A1 - Kalyanikrishna, A1 - Engelhorn, Julia A1 - Farrona, Sara T1 - Looking At the Past and Heading to the Future BT - Meeting Summary of the 6th European Workshop on Plant Chromatin 2019 in Cologne, Germany JF - Frontiers in Plant Science N2 - In June 2019, more than a hundred plant researchers met in Cologne, Germany, for the 6th European Workshop on Plant Chromatin (EWPC). This conference brought together a highly dynamic community of researchers with the common aim to understand how chromatin organization controls gene expression, development, and plant responses to the environment. New evidence showing how epigenetic states are set, perpetuated, and inherited were presented, and novel data related to the three-dimensional organization of chromatin within the nucleus were discussed. At the level of the nucleosome, its composition by different histone variants and their specialized histone deposition complexes were addressed as well as the mechanisms involved in histone post-translational modifications and their role in gene expression. The keynote lecture on plant DNA methylation by Julie Law (SALK Institute) and the tribute session to Lars Hennig, honoring the memory of one of the founders of the EWPC who contributed to promote the plant chromatin and epigenetic field in Europe, added a very special note to this gathering. In this perspective article we summarize some of the most outstanding data and advances on plant chromatin research presented at this workshop. KW - EWPC2019 KW - chromatin KW - epigenetics KW - transcription KW - nucleus Y1 - 2020 U6 - https://doi.org/10.3389/fpls.2019.01795 SN - 1664-462X VL - 10 IS - 1795 SP - 1 EP - 12 PB - Frontiers Media CY - Lausanne 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 - Perrella, Giorgio A1 - Bäurle, Isabel A1 - van Zanten, Martijn T1 - Epigenetic regulation of thermomorphogenesis and heat stress tolerance JF - New phytologist : international journal of plant science N2 - Many environmental conditions fluctuate and organisms need to respond effectively. This is especially true for temperature cues that can change in minutes to seasons and often follow a diurnal rhythm. Plants cannot migrate and most cannot regulate their temperature. Therefore, a broad array of responses have evolved to deal with temperature cues from freezing to heat stress. A particular response to mildly elevated temperatures is called thermomorphogenesis, a suite of morphological adaptations that includes thermonasty, formation of thin leaves and elongation growth of petioles and hypocotyl. Thermomorphogenesis allows for optimal performance in suboptimal temperature conditions by enhancing the cooling capacity. When temperatures rise further, heat stress tolerance mechanisms can be induced that enable the plant to survive the stressful temperature, which typically comprises cellular protection mechanisms and memory thereof. Induction of thermomorphogenesis, heat stress tolerance and stress memory depend on gene expression regulation, governed by diverse epigenetic processes. In this Tansley review we update on the current knowledge of epigenetic regulation of heat stress tolerance and elevated temperature signalling and response, with a focus on thermomorphogenesis regulation and heat stress memory. In particular we highlight the emerging role of H3K4 methylation marks in diverse temperature signalling pathways. KW - chromatin remodelling KW - elevated temperature KW - epigenetics KW - heat stress KW - histone modification KW - memory KW - temperature response KW - thermomorphogenesis Y1 - 2022 U6 - https://doi.org/10.1111/nph.17970 SN - 0028-646X SN - 1469-8137 VL - 234 IS - 4 SP - 1144 EP - 1160 PB - Wiley CY - Hoboken ER -