[{"has_accepted_license":"1","publication":"Cell Systems","month":"11","project":[{"name":"Quantitative analysis of DNA methylation maintenance with chromatin","grant_number":"725746","_id":"62935a00-2b32-11ec-9570-eff30fa39068","call_identifier":"H2020"}],"oa_version":"Published Version","language":[{"iso":"eng"}],"type":"journal_article","date_published":"2023-11-15T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"publication_identifier":{"issn":["2405-4712"],"eissn":["2405-4720"]},"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"file_id":"14580","creator":"dernst","access_level":"open_access","success":1,"relation":"main_file","date_updated":"2023-11-20T11:22:52Z","content_type":"application/pdf","file_name":"2023_CellSystems_Briffa.pdf","date_created":"2023-11-20T11:22:52Z","file_size":5587897,"checksum":"101fdac59e6f1102d68ef91f2b5bd51a"}],"issue":"11","author":[{"full_name":"Briffa, Amy","first_name":"Amy","last_name":"Briffa"},{"first_name":"Elizabeth","last_name":"Hollwey","full_name":"Hollwey, Elizabeth","id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd"},{"full_name":"Shahzad, Zaigham","last_name":"Shahzad","first_name":"Zaigham"},{"full_name":"Moore, Jonathan D.","last_name":"Moore","first_name":"Jonathan D."},{"full_name":"Lyons, David B.","last_name":"Lyons","first_name":"David B."},{"last_name":"Howard","first_name":"Martin","full_name":"Howard, Martin"},{"first_name":"Daniel","last_name":"Zilberman","orcid":"0000-0002-0123-8649","full_name":"Zilberman, Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1"}],"scopus_import":"1","pmid":1,"_id":"14551","intvolume":"        14","title":"Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations","article_processing_charge":"Yes (via OA deal)","department":[{"_id":"DaZi"}],"date_created":"2023-11-19T23:00:54Z","publication_status":"published","file_date_updated":"2023-11-20T11:22:52Z","quality_controlled":"1","ec_funded":1,"page":"953-967","article_type":"original","publisher":"Elsevier","external_id":{"pmid":["37944515"]},"year":"2023","citation":{"apa":"Briffa, A., Hollwey, E., Shahzad, Z., Moore, J. D., Lyons, D. B., Howard, M., &#38; Zilberman, D. (2023). Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. <i>Cell Systems</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">https://doi.org/10.1016/j.cels.2023.10.007</a>","ama":"Briffa A, Hollwey E, Shahzad Z, et al. Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. <i>Cell Systems</i>. 2023;14(11):953-967. doi:<a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">10.1016/j.cels.2023.10.007</a>","ieee":"A. Briffa <i>et al.</i>, “Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations,” <i>Cell Systems</i>, vol. 14, no. 11. Elsevier, pp. 953–967, 2023.","chicago":"Briffa, Amy, Elizabeth Hollwey, Zaigham Shahzad, Jonathan D. Moore, David B. Lyons, Martin Howard, and Daniel Zilberman. “Millennia-Long Epigenetic Fluctuations Generate Intragenic DNA Methylation Variance in Arabidopsis Populations.” <i>Cell Systems</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">https://doi.org/10.1016/j.cels.2023.10.007</a>.","short":"A. Briffa, E. Hollwey, Z. Shahzad, J.D. Moore, D.B. Lyons, M. Howard, D. Zilberman, Cell Systems 14 (2023) 953–967.","mla":"Briffa, Amy, et al. “Millennia-Long Epigenetic Fluctuations Generate Intragenic DNA Methylation Variance in Arabidopsis Populations.” <i>Cell Systems</i>, vol. 14, no. 11, Elsevier, 2023, pp. 953–67, doi:<a href=\"https://doi.org/10.1016/j.cels.2023.10.007\">10.1016/j.cels.2023.10.007</a>.","ista":"Briffa A, Hollwey E, Shahzad Z, Moore JD, Lyons DB, Howard M, Zilberman D. 2023. Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. Cell Systems. 14(11), 953–967."},"date_updated":"2023-11-20T11:24:34Z","abstract":[{"lang":"eng","text":"Methylation of CG dinucleotides (mCGs), which regulates eukaryotic genome functions, is epigenetically propagated by Dnmt1/MET1 methyltransferases. How mCG is established and transmitted across generations despite imperfect enzyme fidelity is unclear. Whether mCG variation in natural populations is governed by genetic or epigenetic inheritance also remains mysterious. Here, we show that MET1 de novo activity, which is enhanced by existing proximate methylation, seeds and stabilizes mCG in Arabidopsis thaliana genes. MET1 activity is restricted by active demethylation and suppressed by histone variant H2A.Z, producing localized mCG patterns. Based on these observations, we develop a stochastic mathematical model that precisely recapitulates mCG inheritance dynamics and predicts intragenic mCG patterns and their population-scale variation given only CG site spacing. Our results demonstrate that intragenic mCG establishment, inheritance, and variance constitute a unified epigenetic process, revealing that intragenic mCG undergoes large, millennia-long epigenetic fluctuations and can therefore mediate evolution on this timescale."}],"day":"15","doi":"10.1016/j.cels.2023.10.007","ddc":["570"],"acknowledgement":"We would like to thank Xiaoqi Feng, Ander Movilla Miangolarra, and Suzanne de Bruijn for discussions. This work was supported by BBSRC Institute Strategic Programme GEN (BB/P013511/1) to M.H. and D.Z. and by a European Research Council grant MaintainMeth (725746) to D.Z.","volume":14},{"volume":81,"ddc":["570"],"year":"2023","citation":{"ama":"Hollwey E, Briffa A, Howard M, Zilberman D. Concepts, mechanisms and implications of long-term epigenetic inheritance. <i>Current Opinion in Genetics and Development</i>. 2023;81(8). doi:<a href=\"https://doi.org/10.1016/j.gde.2023.102087\">10.1016/j.gde.2023.102087</a>","apa":"Hollwey, E., Briffa, A., Howard, M., &#38; Zilberman, D. (2023). Concepts, mechanisms and implications of long-term epigenetic inheritance. <i>Current Opinion in Genetics and Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2023.102087\">https://doi.org/10.1016/j.gde.2023.102087</a>","chicago":"Hollwey, Elizabeth, Amy Briffa, Martin Howard, and Daniel Zilberman. “Concepts, Mechanisms and Implications of Long-Term Epigenetic Inheritance.” <i>Current Opinion in Genetics and Development</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.gde.2023.102087\">https://doi.org/10.1016/j.gde.2023.102087</a>.","ieee":"E. Hollwey, A. Briffa, M. Howard, and D. Zilberman, “Concepts, mechanisms and implications of long-term epigenetic inheritance,” <i>Current Opinion in Genetics and Development</i>, vol. 81, no. 8. Elsevier, 2023.","mla":"Hollwey, Elizabeth, et al. “Concepts, Mechanisms and Implications of Long-Term Epigenetic Inheritance.” <i>Current Opinion in Genetics and Development</i>, vol. 81, no. 8, 102087, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.gde.2023.102087\">10.1016/j.gde.2023.102087</a>.","short":"E. Hollwey, A. Briffa, M. Howard, D. Zilberman, Current Opinion in Genetics and Development 81 (2023).","ista":"Hollwey E, Briffa A, Howard M, Zilberman D. 2023. Concepts, mechanisms and implications of long-term epigenetic inheritance. Current Opinion in Genetics and Development. 81(8), 102087."},"date_updated":"2023-12-13T12:05:31Z","external_id":{"pmid":["37441873"],"isi":["001047020200001"]},"isi":1,"day":"01","doi":"10.1016/j.gde.2023.102087","abstract":[{"text":"Many modes and mechanisms of epigenetic inheritance have been elucidated in eukaryotes. Most of them are relatively short-term, generally not exceeding one or a few organismal generations. However, emerging evidence indicates that one mechanism, cytosine DNA methylation, can mediate epigenetic inheritance over much longer timescales, which are mostly or completely inaccessible in the laboratory. Here we discuss the evidence for, and mechanisms and implications of, such long-term epigenetic inheritance. We argue that compelling evidence supports the long-term epigenetic inheritance of gene body methylation, at least in the model angiosperm Arabidopsis thaliana, and that variation in such methylation can therefore serve as an epigenetic basis for phenotypic variation in natural populations.","lang":"eng"}],"quality_controlled":"1","file_date_updated":"2023-08-07T08:32:26Z","publisher":"Elsevier","article_type":"original","scopus_import":"1","_id":"13965","pmid":1,"issue":"8","author":[{"id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd","full_name":"Hollwey, Elizabeth","first_name":"Elizabeth","last_name":"Hollwey"},{"first_name":"Amy","last_name":"Briffa","full_name":"Briffa, Amy"},{"full_name":"Howard, Martin","first_name":"Martin","last_name":"Howard"},{"full_name":"Zilberman, Daniel","orcid":"0000-0002-0123-8649","last_name":"Zilberman","first_name":"Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1"}],"department":[{"_id":"DaZi"}],"article_processing_charge":"Yes (via OA deal)","date_created":"2023-08-06T22:01:10Z","intvolume":"        81","title":"Concepts, mechanisms and implications of long-term epigenetic inheritance","file":[{"relation":"main_file","success":1,"access_level":"open_access","file_id":"13980","creator":"dernst","date_created":"2023-08-07T08:32:26Z","file_size":2568632,"checksum":"a294cd9506b80ed6ef218ef44ed32765","date_updated":"2023-08-07T08:32:26Z","file_name":"2023_CurrentOpinionGenetics_Hollwey.pdf","content_type":"application/pdf"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2023-08-01T00:00:00Z","publication_identifier":{"eissn":["1879-0380"],"issn":["0959-437X"]},"oa":1,"language":[{"iso":"eng"}],"has_accepted_license":"1","publication":"Current Opinion in Genetics and Development","oa_version":"Published Version","article_number":"102087","month":"08"},{"article_type":"original","publisher":"Elsevier","file_date_updated":"2023-05-11T10:41:42Z","quality_controlled":"1","ec_funded":1,"intvolume":"        42","title":"Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons","department":[{"_id":"DaZi"},{"_id":"XiFe"}],"date_created":"2023-02-23T09:17:44Z","article_processing_charge":"Yes","publication_status":"published","issue":"3","author":[{"first_name":"David B.","last_name":"Lyons","full_name":"Lyons, David B."},{"full_name":"Briffa, Amy","last_name":"Briffa","first_name":"Amy"},{"full_name":"He, Shengbo","first_name":"Shengbo","last_name":"He"},{"full_name":"Choi, Jaemyung","last_name":"Choi","first_name":"Jaemyung"},{"id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd","full_name":"Hollwey, Elizabeth","first_name":"Elizabeth","last_name":"Hollwey"},{"first_name":"Jack","last_name":"Colicchio","full_name":"Colicchio, Jack"},{"last_name":"Anderson","first_name":"Ian","full_name":"Anderson, Ian"},{"id":"e0164712-22ee-11ed-b12a-d80fcdf35958","full_name":"Feng, Xiaoqi","orcid":"0000-0002-4008-1234","last_name":"Feng","first_name":"Xiaoqi"},{"first_name":"Martin","last_name":"Howard","full_name":"Howard, Martin"},{"id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","full_name":"Zilberman, Daniel","orcid":"0000-0002-0123-8649","last_name":"Zilberman","first_name":"Daniel"}],"scopus_import":"1","_id":"12672","ddc":["580"],"acknowledgement":"The authors would like to thank Jasper Rine for advice and mentorship to D.B.L., Lesley Philips, Timothy Wells, Sophie Able, and Christina Wistrom for support with plant growth, and Bhagyshree Jamge and Frédéric Berger for help with analysis of ddm1 × WT RNA-sequencing data. This work was supported by BBSRC Institute Strategic Program GEN (BB/P013511/1) to X.F., M.H., and D.Z., a European Research Council grant MaintainMeth (725746) to D.Z., and a postdoctoral fellowship from the Helen Hay Whitney Foundation to D.B.L.","volume":42,"abstract":[{"lang":"eng","text":"Cytosine methylation within CG dinucleotides (mCG) can be epigenetically inherited over many generations. Such inheritance is thought to be mediated by a semiconservative mechanism that produces binary present/absent methylation patterns. However, we show here that in Arabidopsis thaliana h1ddm1 mutants, intermediate heterochromatic mCG is stably inherited across many generations and is quantitatively associated with transposon expression. We develop a mathematical model that estimates the rates of semiconservative maintenance failure and de novo methylation at each transposon, demonstrating that mCG can be stably inherited at any level via a dynamic balance of these activities. We find that DRM2 – the core methyltransferase of the RNA-directed DNA methylation pathway – catalyzes most of the heterochromatic de novo mCG, with de novo rates orders of magnitude higher than previously thought, whereas chromomethylases make smaller contributions. Our results demonstrate that stable epigenetic inheritance of mCG in plant heterochromatin is enabled by extensive de novo methylation."}],"day":"28","doi":"10.1016/j.celrep.2023.112132","external_id":{"isi":["000944921600001"]},"isi":1,"citation":{"ama":"Lyons DB, Briffa A, He S, et al. Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons. <i>Cell Reports</i>. 2023;42(3). doi:<a href=\"https://doi.org/10.1016/j.celrep.2023.112132\">10.1016/j.celrep.2023.112132</a>","apa":"Lyons, D. B., Briffa, A., He, S., Choi, J., Hollwey, E., Colicchio, J., … Zilberman, D. (2023). Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2023.112132\">https://doi.org/10.1016/j.celrep.2023.112132</a>","ieee":"D. B. Lyons <i>et al.</i>, “Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons,” <i>Cell Reports</i>, vol. 42, no. 3. Elsevier, 2023.","chicago":"Lyons, David B., Amy Briffa, Shengbo He, Jaemyung Choi, Elizabeth Hollwey, Jack Colicchio, Ian Anderson, Xiaoqi Feng, Martin Howard, and Daniel Zilberman. “Extensive de Novo Activity Stabilizes Epigenetic Inheritance of CG Methylation in Arabidopsis Transposons.” <i>Cell Reports</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.celrep.2023.112132\">https://doi.org/10.1016/j.celrep.2023.112132</a>.","short":"D.B. Lyons, A. Briffa, S. He, J. Choi, E. Hollwey, J. Colicchio, I. Anderson, X. Feng, M. Howard, D. Zilberman, Cell Reports 42 (2023).","mla":"Lyons, David B., et al. “Extensive de Novo Activity Stabilizes Epigenetic Inheritance of CG Methylation in Arabidopsis Transposons.” <i>Cell Reports</i>, vol. 42, no. 3, 112132, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.celrep.2023.112132\">10.1016/j.celrep.2023.112132</a>.","ista":"Lyons DB, Briffa A, He S, Choi J, Hollwey E, Colicchio J, Anderson I, Feng X, Howard M, Zilberman D. 2023. Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons. Cell Reports. 42(3), 112132."},"year":"2023","date_updated":"2023-11-02T12:23:45Z","language":[{"iso":"eng"}],"article_number":"112132","month":"03","project":[{"_id":"62935a00-2b32-11ec-9570-eff30fa39068","call_identifier":"H2020","name":"Quantitative analysis of DNA methylation maintenance with chromatin","grant_number":"725746"}],"oa_version":"Published Version","has_accepted_license":"1","publication":"Cell Reports","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","file":[{"date_updated":"2023-05-11T10:41:42Z","content_type":"application/pdf","file_name":"2023_CellReports_Lyons.pdf","date_created":"2023-05-11T10:41:42Z","file_size":8401261,"checksum":"6cbc44fdb18bf18834c9e2a5b9c67123","file_id":"12941","creator":"kschuh","access_level":"open_access","success":1,"relation":"main_file"}],"oa":1,"publication_identifier":{"eissn":["2211-1247"]},"type":"journal_article","date_published":"2023-03-28T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"}}]