{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:45:27Z","timestamp":1789659927638,"version":"4.0.1"},"reference-count":74,"publisher":"National Academy of Sciences","issue":"28","license":[{"start":{"date-parts":[[2019,12,24]],"date-time":"2019-12-24T00:00:00Z","timestamp":1577145600000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["C7027-16G"],"award-info":[{"award-number":["C7027-16G"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["106180141"],"award-info":[{"award-number":["106180141"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003803","name":"University of Hong Kong","doi-asserted-by":"publisher","award":["201308159003"],"award-info":[{"award-number":["201308159003"]}],"id":[{"id":"10.13039\/501100003803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["AoE\/M-06\/08"],"award-info":[{"award-number":["AoE\/M-06\/08"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,7,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Epstein\u2212Barr virus (EBV) infection is implicated in the development of certain cancers; however, the mechanisms by which EBV contributes to the pathogenesis of epithelial cell malignancies remains unclear. This study highlights the association of EBV infection with aberrant modifications in histone bivalent marks, H3K4me3 and H3K27me3, in nasopharyngeal epithelial cells. Down-regulation of the DNA damage repair pathway genes, including\n                    <jats:italic>MLH1<\/jats:italic>\n                    , associated with aberrant histone bivalent marks in a promoter hypermethylation-independent manner, was observed after EBV infection. This finding provides strong evidence linking EBV infection to epigenetic modifications in epithelial cells. This study also suggests that the level of MLH1 may be useful as a potential biomarker to evaluate the responsiveness of nasopharyngeal carcinoma patients to cisplatin-based therapies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1821752116","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T08:50:21Z","timestamp":1561452621000},"page":"14144-14153","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":34,"title":["EBV infection is associated with histone bivalent switch modifications in squamous epithelial cells"],"prefix":"10.1073","volume":"116","author":[{"given":"Merrin Man Long","family":"Leong","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Kwok Leung","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai Wah","family":"Tsao","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"},{"name":"Centre for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Man","family":"Tsang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher W.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infection, Warwick Medical School, The University of Warwick, CV4 7HL Coventry, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Mun Yee Ko","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2559-3626","authenticated-orcid":false,"given":"Maria Li","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"},{"name":"Centre for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong SAR, People\u2019s Republic of China;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,6,24]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(00)00046-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt886"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1503806112"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.5.2689-2697.1992"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909344107"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2015.10.007"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04290"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04802"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.967202"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C400151200"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1076997"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.219626.113"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.041"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3030"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.451"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202637109"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1159\/000486354"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.07.003"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.06.035"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-3147"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000018979.68686.B2"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1273"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3892\/etm_00000017"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2015.10.003"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2016.0270"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00367"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-2194"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27724"},{"key":"e_1_3_3_30_2","first-page":"2125","article-title":"H3K4me3 and Wdr82 are associated with tumor progression and a favorable prognosis in human colorectal cancer","volume":"16","author":"Liu H.","year":"2018","unstructured":"H. Liu, Y. Li, J. Li, Y. Liu, B. Cui, H3K4me3 and Wdr82 are associated with tumor progression and a favorable prognosis in human colorectal cancer. Oncol. Lett. 16, 2125\u20132134 (2018).","journal-title":"Oncol. Lett."},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06768-11"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25173"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.06.031"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.enz.2016.03.003"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121851"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150712543"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-009-8736-z"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874467211205010003"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2013.14.9.5145"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2003.11.003"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.3.2414"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1155\/2004\/305058"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65048-1"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-016-0765-y"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.08.083"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.159"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806437105"},{"key":"e_1_3_3_48_2","first-page":"g2","article-title":"Evidence of Epstein-Barr virus association with head and neck cancers: A review","volume":"82","author":"Prabhu S. R.","year":"2016","unstructured":"S. R. Prabhu, D. F. Wilson, Evidence of Epstein-Barr virus association with head and neck cancers: A review. J. Can. Dent. Assoc. 82, g2 (2016).","journal-title":"J. Can. Dent. Assoc."},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200406000-00013"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.5611"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008434"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809303200"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2014.01.009"},{"key":"e_1_3_3_54_2","first-page":"184","article-title":"[Correlation between DNA damage and EB virus infection in nasopharyngeal carcinoma]","volume":"30","author":"Gou Y.","year":"2014","unstructured":"Y. Gou , [Correlation between DNA damage and EB virus infection in nasopharyngeal carcinoma]. Xibao Yu Fenzi Mianyixue Zazhi 30, 184\u2013187 (2014).","journal-title":"Xibao Yu Fenzi Mianyixue Zazhi"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00430-08"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00958-15"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00053-07"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.11.004"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-262"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3042"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990924)83:1<121::AID-IJC21>3.0.CO;2-F"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12889"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/1746-4811-3-11"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-1"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-232"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990820)84:4<404::AID-IJC13>3.0.CO;2-L"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201205059"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/oncsis.2014.42"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900198106"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1821752116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1821752116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T04:43:08Z","timestamp":1649824988000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1821752116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,24]]},"references-count":74,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2019,7,9]]}},"alternative-id":["10.1073\/pnas.1821752116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1821752116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,24]]},"assertion":[{"value":"2019-06-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}