{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:53:19Z","timestamp":1780433599988,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Industrial production of biologics typically involves the integration of transgenes into host cell genomes, most often Chinese hamster ovary (CHO) cells. Epigenetic control of transgene expression is a major determinant of production titers. Although the cytomegalovirus (CMV) promoter has long been used to drive industrial transgene expression, we found that its associated histones are suboptimally acetylated in CHO cells, providing an opportunity to enhance productivity through epigenetic manipulation. Expression of monoclonal antibody mRNAs increased up to 12\u2010fold when a CRISPR\u2010dCas9 system delivered the catalytic domain of a histone acetyltransferase to the CMV promoter. This effect was far stronger than when promoter DNA was selectively demethylated using dCas9 fused to a 5\u2010methylcytosine dioxygenase. Mechanistically, acetylation\u2010mediated transcriptional activation involved heightened phosphorylation and activity of RNA polymerase II, enabling it to escape promoter\u2010proximal pausing at the transgene. This approach almost doubled the titer and specific productivity of antibody\u2010producing CHO cells, demonstrating the potential for biomanufacturing.<\/jats:p>","DOI":"10.1002\/biot.202400474","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T04:52:37Z","timestamp":1733806357000},"source":"Crossref","is-referenced-by-count":4,"title":["Selective Recruitment of a Synthetic Histone Acetyltransferase Can Boost CHO Cell Productivity"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5590-3907","authenticated-orcid":false,"given":"Sienna P.","family":"Butterfield","sequence":"first","affiliation":[{"name":"Department of Biology University of York  York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3192-0304","authenticated-orcid":false,"given":"Rebecca E.","family":"Sizer","sequence":"additional","affiliation":[{"name":"Department of Biology University of York  York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fay L.","family":"Saunders","sequence":"additional","affiliation":[{"name":"FUJIFILM Diosynth Biotechnologies  Billingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9631-7760","authenticated-orcid":false,"given":"Robert J.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Biology University of York  York UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4305"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01582-x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12896-017-0330-0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2019.01.011"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2020.11.008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1656(99)00044-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.04.004"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.18.2852"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12896-016-0238-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-013-1168-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2016.11.020"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0107-2"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90051-Q"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05915"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25990"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2666"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2022.107924"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2005.16.881"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24485"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201400744"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.23216"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2014.12.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25227"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202200062"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2271"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120096"},{"key":"e_1_2_10_28_1","unstructured":"F. L.Saunders(2011).An investigation into the role of chromatin modifying elements on the production of recombinant antibodies from CHO Cells [Phd The Open University] https:\/\/doi.org\/10.21954\/ou.ro.0000ed85."},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2022.146533"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2022.11.059"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201500159"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28013"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.12.018"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.01.019"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx578"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-019-0275-8"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3199"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2021.04.014"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201700217"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2004.07.012"},{"key":"e_1_2_10_41_1","article-title":"Generation of Genomic Deletions in Mammalian Cell Lines via CRISPR\/Cas9","volume":"95","author":"Bauer D. E.","year":"2015","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.02.008"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a021749"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.04.033"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16182-z"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.8.4629"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes3020320"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.06.027"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(98)80133-0"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.1542"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1753"}],"container-title":["Biotechnology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biot.202400474","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T20:22:14Z","timestamp":1759954934000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/biot.202400474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/biot.202400474"],"URL":"https:\/\/doi.org\/10.1002\/biot.202400474","archive":["Portico"],"relation":{},"ISSN":["1860-6768","1860-7314"],"issn-type":[{"value":"1860-6768","type":"print"},{"value":"1860-7314","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"article-number":"e202400474"}}