[{"license":"https://creativecommons.org/licenses/by/4.0/","publication_status":"published","oa":1,"file_date_updated":"2023-11-20T11:22:52Z","volume":14,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"issue":"11","article_processing_charge":"Yes (via OA deal)","file":[{"creator":"dernst","file_size":5587897,"file_name":"2023_CellSystems_Briffa.pdf","access_level":"open_access","date_updated":"2023-11-20T11:22:52Z","checksum":"101fdac59e6f1102d68ef91f2b5bd51a","file_id":"14580","relation":"main_file","content_type":"application/pdf","success":1,"date_created":"2023-11-20T11:22:52Z"}],"_id":"14551","date_published":"2023-11-15T00:00:00Z","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."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2023-11-20T11:24:34Z","external_id":{"pmid":["37944515"]},"scopus_import":"1","publication_identifier":{"eissn":["2405-4720"],"issn":["2405-4712"]},"article_type":"original","has_accepted_license":"1","oa_version":"Published Version","year":"2023","publisher":"Elsevier","department":[{"_id":"DaZi"}],"quality_controlled":"1","publication":"Cell Systems","intvolume":"        14","status":"public","page":"953-967","month":"11","date_created":"2023-11-19T23:00:54Z","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.","pmid":1,"project":[{"call_identifier":"H2020","_id":"62935a00-2b32-11ec-9570-eff30fa39068","name":"Quantitative analysis of DNA methylation maintenance with chromatin","grant_number":"725746"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cels.2023.10.007","ddc":["570"],"ec_funded":1,"citation":{"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>.","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.","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.","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>.","short":"A. Briffa, E. Hollwey, Z. Shahzad, J.D. Moore, D.B. Lyons, M. Howard, D. Zilberman, Cell Systems 14 (2023) 953–967.","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>","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>"},"title":"Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations","day":"15","author":[{"last_name":"Briffa","first_name":"Amy","full_name":"Briffa, Amy"},{"id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd","full_name":"Hollwey, Elizabeth","first_name":"Elizabeth","last_name":"Hollwey"},{"full_name":"Shahzad, Zaigham","first_name":"Zaigham","last_name":"Shahzad"},{"last_name":"Moore","first_name":"Jonathan D.","full_name":"Moore, Jonathan D."},{"first_name":"David B.","full_name":"Lyons, David B.","last_name":"Lyons"},{"last_name":"Howard","full_name":"Howard, Martin","first_name":"Martin"},{"last_name":"Zilberman","first_name":"Daniel","full_name":"Zilberman, Daniel","orcid":"0000-0002-0123-8649","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1"}],"type":"journal_article"},{"isi":1,"publisher":"Elsevier","status":"public","intvolume":"        42","publication":"Cell Reports","department":[{"_id":"DaZi"},{"_id":"XiFe"}],"quality_controlled":"1","date_created":"2023-02-23T09:17:44Z","month":"03","project":[{"grant_number":"725746","name":"Quantitative analysis of DNA methylation maintenance with chromatin","_id":"62935a00-2b32-11ec-9570-eff30fa39068","call_identifier":"H2020"}],"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.","doi":"10.1016/j.celrep.2023.112132","ddc":["580"],"language":[{"iso":"eng"}],"title":"Extensive de novo activity stabilizes epigenetic inheritance of CG methylation in Arabidopsis transposons","citation":{"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>.","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>.","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.","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.","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>","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)."},"ec_funded":1,"type":"journal_article","author":[{"first_name":"David B.","full_name":"Lyons, David B.","last_name":"Lyons"},{"first_name":"Amy","full_name":"Briffa, Amy","last_name":"Briffa"},{"first_name":"Shengbo","full_name":"He, Shengbo","last_name":"He"},{"full_name":"Choi, Jaemyung","first_name":"Jaemyung","last_name":"Choi"},{"id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd","last_name":"Hollwey","full_name":"Hollwey, Elizabeth","first_name":"Elizabeth"},{"full_name":"Colicchio, Jack","first_name":"Jack","last_name":"Colicchio"},{"last_name":"Anderson","first_name":"Ian","full_name":"Anderson, Ian"},{"full_name":"Feng, Xiaoqi","first_name":"Xiaoqi","last_name":"Feng","orcid":"0000-0002-4008-1234","id":"e0164712-22ee-11ed-b12a-d80fcdf35958"},{"full_name":"Howard, Martin","first_name":"Martin","last_name":"Howard"},{"full_name":"Zilberman, Daniel","first_name":"Daniel","last_name":"Zilberman","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","orcid":"0000-0002-0123-8649"}],"day":"28","oa":1,"publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"volume":42,"file_date_updated":"2023-05-11T10:41:42Z","article_processing_charge":"Yes","issue":"3","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."}],"_id":"12672","date_published":"2023-03-28T00:00:00Z","article_number":"112132","file":[{"checksum":"6cbc44fdb18bf18834c9e2a5b9c67123","access_level":"open_access","date_updated":"2023-05-11T10:41:42Z","file_size":8401261,"creator":"kschuh","file_name":"2023_CellReports_Lyons.pdf","date_created":"2023-05-11T10:41:42Z","success":1,"relation":"main_file","file_id":"12941","content_type":"application/pdf"}],"publication_identifier":{"eissn":["2211-1247"]},"external_id":{"isi":["000944921600001"]},"scopus_import":"1","date_updated":"2023-11-02T12:23:45Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","oa_version":"Published Version","year":"2023","article_type":"original"},{"isi":1,"publisher":"eLife Sciences Publications","status":"public","intvolume":"        10","publication":"eLife","department":[{"_id":"DaZi"}],"quality_controlled":"1","date_created":"2021-12-10T13:12:08Z","month":"12","pmid":1,"project":[{"_id":"62935a00-2b32-11ec-9570-eff30fa39068","call_identifier":"H2020","name":"Quantitative analysis of DNA methylation maintenance with chromatin","grant_number":"725746"}],"acknowledgement":"We thank X Feng for helpful comments on the manuscript. This work was supported by a European Research Council grant MaintainMeth (725746) to DZ.","doi":"10.7554/elife.72676","ddc":["570"],"keyword":["genetics and molecular biology"],"language":[{"iso":"eng"}],"title":"Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin","citation":{"apa":"Choi, J., Lyons, D. B., &#38; Zilberman, D. (2021). Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.72676\">https://doi.org/10.7554/elife.72676</a>","ama":"Choi J, Lyons DB, Zilberman D. Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.72676\">10.7554/elife.72676</a>","short":"J. Choi, D.B. Lyons, D. Zilberman, ELife 10 (2021).","mla":"Choi, Jaemyung, et al. “Histone H1 Prevents Non-CG Methylation-Mediated Small RNA Biogenesis in Arabidopsis Heterochromatin.” <i>ELife</i>, vol. 10, e72676, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.72676\">10.7554/elife.72676</a>.","ieee":"J. Choi, D. B. Lyons, and D. Zilberman, “Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ista":"Choi J, Lyons DB, Zilberman D. 2021. Histone H1 prevents non-CG methylation-mediated small RNA biogenesis in Arabidopsis heterochromatin. eLife. 10, e72676.","chicago":"Choi, Jaemyung, David B Lyons, and Daniel Zilberman. “Histone H1 Prevents Non-CG Methylation-Mediated Small RNA Biogenesis in Arabidopsis Heterochromatin.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.72676\">https://doi.org/10.7554/elife.72676</a>."},"ec_funded":1,"author":[{"last_name":"Choi","full_name":"Choi, Jaemyung","first_name":"Jaemyung"},{"first_name":"David B","full_name":"Lyons, David B","last_name":"Lyons"},{"full_name":"Zilberman, Daniel","first_name":"Daniel","last_name":"Zilberman","orcid":"0000-0002-0123-8649","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1"}],"type":"journal_article","day":"01","oa":1,"publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"volume":10,"file_date_updated":"2022-05-16T10:42:22Z","article_processing_charge":"No","date_published":"2021-12-01T00:00:00Z","_id":"10533","abstract":[{"lang":"eng","text":"Flowering plants utilize small RNA molecules to guide DNA methyltransferases to genomic sequences. This RNA-directed DNA methylation (RdDM) pathway preferentially targets euchromatic transposable elements. However, RdDM is thought to be recruited by methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin. How RdDM is targeted to euchromatin despite an affinity for H3K9me is unclear. Here we show that loss of histone H1 enhances heterochromatic RdDM, preferentially at nucleosome linker DNA. Surprisingly, this does not require SHH1, the RdDM component that binds H3K9me. Furthermore, H3K9me is dispensable for RdDM, as is CG DNA methylation. Instead, we find that non-CG methylation is specifically associated with small RNA biogenesis, and without H1 small RNA production quantitatively expands to non-CG methylated loci. Our results demonstrate that H1 enforces the separation of euchromatic and heterochromatic DNA methylation pathways by excluding the small RNA-generating branch of RdDM from non-CG methylated heterochromatin."}],"file":[{"file_size":2715200,"creator":"dernst","file_name":"2021_eLife_Choi.pdf","checksum":"22ed4c55fb550f6da02ae55c359be651","access_level":"open_access","date_updated":"2022-05-16T10:42:22Z","relation":"main_file","file_id":"11384","content_type":"application/pdf","date_created":"2022-05-16T10:42:22Z","success":1}],"article_number":"e72676","publication_identifier":{"issn":["2050-084X"]},"external_id":{"isi":["000754832000001"],"pmid":["34850679"]},"scopus_import":"1","date_updated":"2023-08-17T06:21:08Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","year":"2021","has_accepted_license":"1","article_type":"original"}]