[{"file_date_updated":"2023-11-20T11:22:52Z","ec_funded":1,"license":"https://creativecommons.org/licenses/by/4.0/","author":[{"full_name":"Briffa, Amy","last_name":"Briffa","first_name":"Amy"},{"full_name":"Hollwey, Elizabeth","first_name":"Elizabeth","last_name":"Hollwey","id":"b8c4f54b-e484-11eb-8fdc-a54df64ef6dd"},{"last_name":"Shahzad","first_name":"Zaigham","full_name":"Shahzad, Zaigham"},{"first_name":"Jonathan D.","last_name":"Moore","full_name":"Moore, Jonathan D."},{"first_name":"David B.","last_name":"Lyons","full_name":"Lyons, David B."},{"first_name":"Martin","last_name":"Howard","full_name":"Howard, Martin"},{"full_name":"Zilberman, Daniel","last_name":"Zilberman","first_name":"Daniel","orcid":"0000-0002-0123-8649","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1"}],"date_updated":"2023-11-20T11:24:34Z","date_created":"2023-11-19T23:00:54Z","volume":14,"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.","year":"2023","pmid":1,"publication_status":"published","department":[{"_id":"DaZi"}],"publisher":"Elsevier","month":"11","publication_identifier":{"issn":["2405-4712"],"eissn":["2405-4720"]},"doi":"10.1016/j.cels.2023.10.007","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["37944515"]},"oa":1,"quality_controlled":"1","project":[{"name":"Quantitative analysis of DNA methylation maintenance with chromatin","call_identifier":"H2020","grant_number":"725746","_id":"62935a00-2b32-11ec-9570-eff30fa39068"}],"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."}],"issue":"11","type":"journal_article","oa_version":"Published Version","file":[{"creator":"dernst","file_size":5587897,"content_type":"application/pdf","file_name":"2023_CellSystems_Briffa.pdf","access_level":"open_access","date_updated":"2023-11-20T11:22:52Z","date_created":"2023-11-20T11:22:52Z","success":1,"checksum":"101fdac59e6f1102d68ef91f2b5bd51a","file_id":"14580","relation":"main_file"}],"_id":"14551","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations","ddc":["570"],"status":"public","intvolume":" 14","day":"15","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","scopus_import":"1","date_published":"2023-11-15T00:00:00Z","publication":"Cell Systems","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.” Cell Systems. Elsevier, 2023. https://doi.org/10.1016/j.cels.2023.10.007.","mla":"Briffa, Amy, et al. “Millennia-Long Epigenetic Fluctuations Generate Intragenic DNA Methylation Variance in Arabidopsis Populations.” Cell Systems, vol. 14, no. 11, Elsevier, 2023, pp. 953–67, doi:10.1016/j.cels.2023.10.007.","short":"A. Briffa, E. Hollwey, Z. Shahzad, J.D. Moore, D.B. Lyons, M. Howard, D. Zilberman, Cell Systems 14 (2023) 953–967.","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 et al., “Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations,” Cell Systems, vol. 14, no. 11. Elsevier, pp. 953–967, 2023.","apa":"Briffa, A., Hollwey, E., Shahzad, Z., Moore, J. D., Lyons, D. B., Howard, M., & Zilberman, D. (2023). Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. Cell Systems. Elsevier. https://doi.org/10.1016/j.cels.2023.10.007","ama":"Briffa A, Hollwey E, Shahzad Z, et al. Millennia-long epigenetic fluctuations generate intragenic DNA methylation variance in Arabidopsis populations. Cell Systems. 2023;14(11):953-967. doi:10.1016/j.cels.2023.10.007"},"article_type":"original","page":"953-967"},{"ec_funded":1,"department":[{"_id":"SiHi"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"acknowledgement":"D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b] life science call grant (C13-002) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program 725780 LinPro to S.H.","year":"2022","volume":13,"date_updated":"2023-08-03T07:19:43Z","date_created":"2022-06-19T22:01:57Z","author":[{"full_name":"Anderson, Donovan J.","first_name":"Donovan J.","last_name":"Anderson"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian"},{"first_name":"Aaron","last_name":"Mckenna","full_name":"Mckenna, Aaron"},{"last_name":"Shendure","first_name":"Jay","full_name":"Shendure, Jay"},{"full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","last_name":"Hippenmeyer","first_name":"Simon"},{"full_name":"Horwitz, Marshall S.","first_name":"Marshall S.","last_name":"Horwitz"}],"publication_identifier":{"issn":["2405-4712"],"eissn":["2405-4720"]},"month":"06","project":[{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"name":"Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain","grant_number":"LS13-002","_id":"25D92700-B435-11E9-9278-68D0E5697425"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000814124400002"],"pmid":["35452605"]},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1016/j.cels.2022.03.006","open_access":"1"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.cels.2022.03.006","type":"journal_article","issue":"6","abstract":[{"text":"Mutations are acquired frequently, such that each cell's genome inscribes its history of cell divisions. Common genomic alterations involve loss of heterozygosity (LOH). LOH accumulates throughout the genome, offering large encoding capacity for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq) of mouse brain cells, we found that LOH events spanning multiple genes are revealed as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide variants (SNVs). We simultaneously inferred cell lineage and marked developmental time points based on X chromosome inactivation and the total number of LOH events while identifying cell types from gene expression patterns. Our results are consistent with progenitor cells giving rise to multiple cortical cell types through stereotyped expansion and distinct waves of neurogenesis. This type of retrospective analysis could be incorporated into scRNA-seq pipelines and, compared with experimental approaches for determining lineage in model organisms, is applicable where genetic engineering is prohibited, such as humans.","lang":"eng"}],"intvolume":" 13","status":"public","title":"Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"11449","oa_version":"Published Version","scopus_import":"1","article_processing_charge":"No","day":"15","page":"438-453.e5","article_type":"original","citation":{"chicago":"Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems. Elsevier, 2022. https://doi.org/10.1016/j.cels.2022.03.006.","short":"D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz, Cell Systems 13 (2022) 438–453.e5.","mla":"Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems, vol. 13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:10.1016/j.cels.2022.03.006.","ieee":"D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M. S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development,” Cell Systems, vol. 13, no. 6. Elsevier, p. 438–453.e5, 2022.","apa":"Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., & Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. Elsevier. https://doi.org/10.1016/j.cels.2022.03.006","ista":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 13(6), 438–453.e5.","ama":"Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical development. Cell Systems. 2022;13(6):438-453.e5. doi:10.1016/j.cels.2022.03.006"},"publication":"Cell Systems","date_published":"2022-06-15T00:00:00Z"}]