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The viral genome forms the basis for chronic infection and has been shown to be subject to regulation by epigenetic mechanisms, such as posttranslational modification of histone proteins. Here, we confirm and expand on previous results by adapting a high-resolution technique for analysis of histone modifications for use with patient-derived fine-needle liver biopsy specimens. Our work highlights that the situation\n            <jats:italic>in vivo<\/jats:italic>\n            is more complex than predicted by current\n            <jats:italic>in vitro<\/jats:italic>\n            models, for example, by suggesting a novel, noncanonical role of the histone modification H3K9me3 in the HBV life cycle. Importantly, enabling the use of fine-needle liver biopsy specimens for such high-resolution analyses may facilitate further research into the epigenetic regulation of the HBV genome.\n          <\/jats:p>","DOI":"10.1128\/jvi.02036-18","type":"journal-article","created":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T14:38:03Z","timestamp":1550500683000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Mapping the Heterogeneity of Histone Modifications on Hepatitis B Virus DNA Using Liver Needle Biopsies Obtained from Chronically Infected Patients"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5095-8493","authenticated-orcid":false,"given":"Tobias","family":"Flecken","sequence":"first","affiliation":[{"name":"Novartis Institutes for Biomedical Research, Infectious Diseases, Emeryville, California, USA"},{"name":"Novartis Institutes for Biomedical Research, CBT Data Sciences, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Anne","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Skewes-Cox","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, CBT Data Sciences, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Barkan","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, CBT Data Sciences, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-4894","authenticated-orcid":false,"given":"Markus H.","family":"Heim","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland"},{"name":"Clinic of Gastroenterology and Hepatology, University Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan F.","family":"Wieland","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan M.","family":"Holdorf","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research, Infectious Diseases, Emeryville, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60220-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22898"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/v9040075"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0241"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309809"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.22"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01703079"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.4481"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.05.022"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.001"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518090112"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22930"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.3.1255-1262.1991"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.009"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.06.023"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29912"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.042"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1345717"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-017-2454-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/282615a0"},{"key":"e_1_3_3_23_2","first-page":"2124","article-title":"Establishment of a continuously growing cell line from primary carcinoma of the liver","volume":"50","author":"Alexander JJ","year":"1976","unstructured":"Alexander JJ, Bey EM, Geddes EW, Lecatsas G. 1976. 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