Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in Arabidopsis
Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has bee...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2018-01, Vol.115 (5), p.E1069-E1074 |
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| creator | Zhang, Yu Harris, C. Jake Liu, Qikun Liu, Wanlu Ausin, Israel Long, Yanping Xiao, Lidan Feng, Li Chen, Xu Xie, Yubin Chen, Xinyuan Zhan, Lingyu Feng, Suhua Li, Jingyi Jessica 李婧翌 Wang, Haifeng Zhai, Jixian Jacobsen, Steven E. |
| description | Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored. Here we reprocessed the raw data of over 500 publicly available Arabidopsis WGBS libraries from various mutant backgrounds, tissue types, and stress treatments and also filtered them based on sequencing depth and efficiency of bisulfite conversion. This enabled us to identify high-confidence differentially methylated regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type controls. We developed statistical and quantitative measurements to analyze the overlapping of DMRs and to cluster libraries based on their effect on DNA methylation. In addition to confirming existing relationships, we revealed unanticipated connections between well-known genes. For instance, MET1 and CMT3 were found to be required for the maintenance of asymmetric CHH methylation at nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative methylome approach has established a framework for extracting biological insights via large-scale comparison of methylomes and can also be adopted for other genomics datasets. |
| doi_str_mv | 10.1073/pnas.1716300115 |
| format | Article |
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Jake ; Liu, Qikun ; Liu, Wanlu ; Ausin, Israel ; Long, Yanping ; Xiao, Lidan ; Feng, Li ; Chen, Xu ; Xie, Yubin ; Chen, Xinyuan ; Zhan, Lingyu ; Feng, Suhua ; Li, Jingyi Jessica ; 李婧翌 ; Wang, Haifeng ; Zhai, Jixian ; Jacobsen, Steven E.</creator><creatorcontrib>Zhang, Yu ; Harris, C. Jake ; Liu, Qikun ; Liu, Wanlu ; Ausin, Israel ; Long, Yanping ; Xiao, Lidan ; Feng, Li ; Chen, Xu ; Xie, Yubin ; Chen, Xinyuan ; Zhan, Lingyu ; Feng, Suhua ; Li, Jingyi Jessica ; 李婧翌 ; Wang, Haifeng ; Zhai, Jixian ; Jacobsen, Steven E.</creatorcontrib><description>Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored. Here we reprocessed the raw data of over 500 publicly available Arabidopsis WGBS libraries from various mutant backgrounds, tissue types, and stress treatments and also filtered them based on sequencing depth and efficiency of bisulfite conversion. This enabled us to identify high-confidence differentially methylated regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type controls. We developed statistical and quantitative measurements to analyze the overlapping of DMRs and to cluster libraries based on their effect on DNA methylation. In addition to confirming existing relationships, we revealed unanticipated connections between well-known genes. For instance, MET1 and CMT3 were found to be required for the maintenance of asymmetric CHH methylation at nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative methylome approach has established a framework for extracting biological insights via large-scale comparison of methylomes and can also be adopted for other genomics datasets.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1716300115</identifier><identifier>PMID: 29339507</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Arabidopsis ; Biological Sciences ; Bisulfite ; Comparative analysis ; Confidence ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA sequencing ; Epigenetics ; Flowers & plants ; Gene expression ; Genes ; Genomics ; Heterochromatin ; PNAS Plus ; Regulatory mechanisms (biology)</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2018-01, Vol.115 (5), p.E1069-E1074</ispartof><rights>Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright © 2018 the Author(s). Published by PNAS.</rights><rights>Copyright National Academy of Sciences Jan 30, 2018</rights><rights>Copyright © 2018 the Author(s). Published by PNAS. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-9b0423193d34b44d1639ba35b3d909a73729f3f6e68411891f67c08202eb24ae3</citedby><cites>FETCH-LOGICAL-c443t-9b0423193d34b44d1639ba35b3d909a73729f3f6e68411891f67c08202eb24ae3</cites><orcidid>0000-0002-9288-5648</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26507311$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26507311$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29339507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Harris, C. Jake</creatorcontrib><creatorcontrib>Liu, Qikun</creatorcontrib><creatorcontrib>Liu, Wanlu</creatorcontrib><creatorcontrib>Ausin, Israel</creatorcontrib><creatorcontrib>Long, Yanping</creatorcontrib><creatorcontrib>Xiao, Lidan</creatorcontrib><creatorcontrib>Feng, Li</creatorcontrib><creatorcontrib>Chen, Xu</creatorcontrib><creatorcontrib>Xie, Yubin</creatorcontrib><creatorcontrib>Chen, Xinyuan</creatorcontrib><creatorcontrib>Zhan, Lingyu</creatorcontrib><creatorcontrib>Feng, Suhua</creatorcontrib><creatorcontrib>Li, Jingyi Jessica</creatorcontrib><creatorcontrib>李婧翌</creatorcontrib><creatorcontrib>Wang, Haifeng</creatorcontrib><creatorcontrib>Zhai, Jixian</creatorcontrib><creatorcontrib>Jacobsen, Steven E.</creatorcontrib><title>Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in Arabidopsis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored. Here we reprocessed the raw data of over 500 publicly available Arabidopsis WGBS libraries from various mutant backgrounds, tissue types, and stress treatments and also filtered them based on sequencing depth and efficiency of bisulfite conversion. This enabled us to identify high-confidence differentially methylated regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type controls. We developed statistical and quantitative measurements to analyze the overlapping of DMRs and to cluster libraries based on their effect on DNA methylation. In addition to confirming existing relationships, we revealed unanticipated connections between well-known genes. For instance, MET1 and CMT3 were found to be required for the maintenance of asymmetric CHH methylation at nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative methylome approach has established a framework for extracting biological insights via large-scale comparison of methylomes and can also be adopted for other genomics datasets.</description><subject>Arabidopsis</subject><subject>Biological Sciences</subject><subject>Bisulfite</subject><subject>Comparative analysis</subject><subject>Confidence</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA sequencing</subject><subject>Epigenetics</subject><subject>Flowers & plants</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genomics</subject><subject>Heterochromatin</subject><subject>PNAS Plus</subject><subject>Regulatory mechanisms (biology)</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpdkc-L1DAUx4Mo7rh69qQUvHjp7suPNs1FWAZdhQEveg5p-jrN0CY1aQf2vzfDjLvq6cH7fvLlffMl5C2FGwqS387epBsqac0BKK2ekQ0FRctaKHhONgBMlo1g4oq8SukAAKpq4CW5YopzVYHckGFn4h7LZM2IhQ3TbKJZ3BELnN0efZicTUXEI5oxFYPDaKIdXKbzcr-OmQ2-CH3hgy-398WEy_Bw2Tpf3EXTui7MyaXX5EWfPfDNZV6Tn18-_9h-LXff779t73alFYIvpWpBME4V77hohehyMtUaXrW8U6CM5JKpnvc11o2gtFG0r6WFhgHDlgmD_Jp8OvvOazthZ9Ev0Yx6jm4y8UEH4_S_ineD3oejrqRqeA3Z4OPFIIZfK6ZFTy5ZHEfjMaxJU9WoSgmQLKMf_kMPYY0-x9Ms_z2AkFWdqdszZWNIKWL_eAwFfWpRn1rUTy3mF-__zvDI_6ktA-_OwCEtIT7p9UmklP8GCpKjQA</recordid><startdate>20180130</startdate><enddate>20180130</enddate><creator>Zhang, Yu</creator><creator>Harris, C. 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Jake</au><au>Liu, Qikun</au><au>Liu, Wanlu</au><au>Ausin, Israel</au><au>Long, Yanping</au><au>Xiao, Lidan</au><au>Feng, Li</au><au>Chen, Xu</au><au>Xie, Yubin</au><au>Chen, Xinyuan</au><au>Zhan, Lingyu</au><au>Feng, Suhua</au><au>Li, Jingyi Jessica</au><au>李婧翌</au><au>Wang, Haifeng</au><au>Zhai, Jixian</au><au>Jacobsen, Steven E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in Arabidopsis</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2018-01-30</date><risdate>2018</risdate><volume>115</volume><issue>5</issue><spage>E1069</spage><epage>E1074</epage><pages>E1069-E1074</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. 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In addition to confirming existing relationships, we revealed unanticipated connections between well-known genes. For instance, MET1 and CMT3 were found to be required for the maintenance of asymmetric CHH methylation at nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative methylome approach has established a framework for extracting biological insights via large-scale comparison of methylomes and can also be adopted for other genomics datasets.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>29339507</pmid><doi>10.1073/pnas.1716300115</doi><orcidid>https://orcid.org/0000-0002-9288-5648</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Arabidopsis Biological Sciences Bisulfite Comparative analysis Confidence Deoxyribonucleic acid DNA DNA methylation DNA sequencing Epigenetics Flowers & plants Gene expression Genes Genomics Heterochromatin PNAS Plus Regulatory mechanisms (biology) |
| title | Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in Arabidopsis |
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