{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:45:50Z","timestamp":1792403150103,"version":"4.4.0"},"reference-count":113,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006106","name":"Austrian Centre of Industrial Biotechnology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006106","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Metabolic Engineering"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.ymben.2021.04.014","type":"journal-article","created":{"date-parts":[[2021,5,16]],"date-time":"2021-05-16T05:11:51Z","timestamp":1621141911000},"page":"268-282","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"special_numbering":"C","title":["Enhanced targeted DNA methylation of the CMV and endogenous promoters with dCas9-DNMT3A3L entails distinct subsequent histone modification changes in CHO cells"],"prefix":"10.1016","volume":"66","author":[{"given":"Nicolas","family":"Marx","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heena","family":"Dhiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6104-7342","authenticated-orcid":false,"given":"Valerie","family":"Schmieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4582-3652","authenticated-orcid":false,"given":"Catarina Martins","family":"Freire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ly Ngoc","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8939-0951","authenticated-orcid":false,"given":"Gerald","family":"Klanert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-9338","authenticated-orcid":false,"given":"Nicole","family":"Borth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymben.2021.04.014_bib1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ymben.2021.04.014_bib2","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/bit.26231","article-title":"A framework to quantify karyotype variation associated with CHO cell line instability at a single-cell level","volume":"114","author":"Baik","year":"2017","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib3","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700230","article-title":"Growth rate changes in CHO host cells are associated with karyotypic heterogeneity","volume":"13","author":"Baik","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/gm346","article-title":"H3K4me3 inversely correlates with DNA methylation at a large class of non-CpG-island-containing start sites","volume":"4","author":"Balasubramanian","year":"2012","journal-title":"Genome Med."},{"key":"10.1016\/j.ymben.2021.04.014_bib5","article-title":"Generation of genomic deletions in mammalian cell lines via CRISPR\/Cas9","author":"Bauer","year":"2014","journal-title":"J. Vis. Exp. JoVE"},{"key":"10.1016\/j.ymben.2021.04.014_bib6","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s00253-011-3806-1","article-title":"Effects of high passage cultivation on CHO cells: a global analysis","volume":"94","author":"Beckmann","year":"2012","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib7","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1074\/jbc.M113.523209","article-title":"The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA","volume":"289","author":"Berkyurek","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymben.2021.04.014_bib8","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1002\/biot.201000095","article-title":"CHO-K1 host cells adapted to growth in glutamine-free medium by FACS-assisted evolution","volume":"5","author":"Bort","year":"2010","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0304-4165(00)00023-4","article-title":"A new Chinese hamster ovary cell line expressing \u03b12,6-sialyltransferase used as universal host for the production of human-like sialylated recombinant glycoproteins","volume":"1474","author":"Bragonzi","year":"2000","journal-title":"Biochim. Biophys. Acta BBA - Gen. Subj."},{"key":"10.1016\/j.ymben.2021.04.014_bib10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/jgm.516","article-title":"Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle","volume":"6","author":"Brooks","year":"2004","journal-title":"J. Gene Med."},{"key":"10.1016\/j.ymben.2021.04.014_bib11","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1002\/bit.25227","article-title":"Synthetic promoters for CHO cell engineering","volume":"111","author":"Brown","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib12","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/biot.201400744","article-title":"NF-\u03baB, CRE and YY1 elements are key functional regulators of CMV promoter-driven transient gene expression in CHO cells","volume":"10","author":"Brown","year":"2015","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib13","article-title":"Chapter 7 - the DNMT3 Family of Mammalian De Novo DNA Methyltransferases","volume":"vol. 101 255-285","author":"Ch\u00e9din","year":"2011"},{"key":"10.1016\/j.ymben.2021.04.014_bib14","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1007\/s00253-017-8331-4","article-title":"Genetic analysis of heterogeneous sub-clones in recombinant Chinese hamster ovary cells","volume":"101","author":"Chen","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib15","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1016\/j.csbj.2020.11.008","article-title":"Predicting favorable landing pads for targeted integrations in Chinese hamster ovary cell lines by learning stability characteristics from random transgene integrations","volume":"18","author":"Dhiman","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib16","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/bit.24367","article-title":"Early prediction of instability of Chinese hamster ovary cell lines expressing recombinant antibodies and antibody-fusion proteins","volume":"109","author":"Dorai","year":"2012","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib17","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/(SICI)1097-0290(20000720)69:2<204::AID-BIT9>3.0.CO;2-Z","article-title":"Limitations to the amplification and stability of human tissue-type plasminogen activator expression by Chinese hamster ovary cells","volume":"69","author":"Fann","year":"2000","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib18","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1002\/bit.25990","article-title":"Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time","volume":"113","author":"Feichtinger","year":"2016","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib19","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nmeth.4042","article-title":"Complex transcriptional modulation with orthogonal and inducible dCas9 regulators","volume":"13","author":"Gao","year":"2016","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymben.2021.04.014_bib20","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.cell.2013.06.044","article-title":"CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes","volume":"154","author":"Gilbert","year":"2013","journal-title":"Cell"},{"key":"10.1016\/j.ymben.2021.04.014_bib21","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1002\/biot.201500027","article-title":"One-step generation of triple knockout CHO cell lines using CRISPR\/Cas9 and fluorescent enrichment","volume":"10","author":"Grav","year":"2015","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib22","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/nature13899","article-title":"Structural insight into autoinhibition and histone H3-induced activation of DNMT3A","volume":"517","author":"Guo","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.ymben.2021.04.014_bib23","doi-asserted-by":"crossref","first-page":"5181","DOI":"10.1038\/s41598-020-62035-6","article-title":"Targeted DNA demethylation of the Fgf21 promoter by CRISPR\/dCas9-mediated epigenome editing","volume":"10","author":"Hanzawa","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymben.2021.04.014_bib24","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1002\/bit.24428","article-title":"Transgene copy number distribution profiles in recombinant CHO cell lines revealed by single cell analyses","volume":"109","author":"He","year":"2012","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/bit.26891","article-title":"Epigenetic regulation of gene expression in Chinese Hamster Ovary cells in response to the changing environment of a batch culture","volume":"116","author":"Hernandez","year":"2019","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib26","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s10529-014-1523-4","article-title":"Identifying and engineering promoters for high level and sustainable therapeutic recombinant protein production in cultured mammalian cells","volume":"36","author":"Ho","year":"2014","journal-title":"Biotechnol. Lett."},{"key":"10.1016\/j.ymben.2021.04.014_bib27","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/nar\/gky1191","article-title":"A tightly regulated and adjustable CRISPR-dCas9 based AND gate in yeast","volume":"47","author":"Hofmann","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib28","doi-asserted-by":"crossref","DOI":"10.1186\/s12896-015-0218-9","article-title":"Transcriptome study and identification of potential marker genes related to the stable expression of recombinant proteins in CHO clones","volume":"15","author":"Jamnikar","year":"2015","journal-title":"BMC Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature06146","article-title":"Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation","volume":"449","author":"Jia","year":"2007","journal-title":"Nature"},{"key":"10.1016\/j.ymben.2021.04.014_bib30","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1093\/nar\/gkn747","article-title":"Formation of nucleoprotein filaments by mammalian DNA methyltransferase Dnmt3a in complex with regulator Dnmt3L","volume":"36","author":"Jurkowska","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib31","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nmeth.3325","article-title":"Functional annotation of native enhancers with a Cas9 -histone demethylase fusion","volume":"12","author":"Kearns","year":"2015","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymben.2021.04.014_bib32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/(SICI)1097-0290(19980405)58:1<73::AID-BIT8>3.0.CO;2-R","article-title":"Characterization of chimeric antibody producing CHO cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure","volume":"58","author":"Kim","year":"1998","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib33","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/(SICI)1097-0290(19981220)60:6<679::AID-BIT5>3.0.CO;2-Q","article-title":"Clonal variability within dihydrofolate reductase-mediated gene amplified Chinese hamster ovary cells: stability in the absence of selective pressure","volume":"60","author":"Kim","year":"1998","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib34","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1002\/bit.23189","article-title":"A mechanistic understanding of production instability in CHO cell lines expressing recombinant monoclonal antibodies","volume":"108","author":"Kim","year":"2011","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib35","doi-asserted-by":"crossref","first-page":"7214","DOI":"10.1073\/pnas.1821740116","article-title":"A CRISPR\/Cas9-based central processing unit to program complex logic computation in human cells","volume":"116","author":"Kim","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.ymben.2021.04.014_bib36","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.celrep.2016.08.083","article-title":"Reversible regulation of promoter and enhancer histone landscape by DNA methylation in mouse embryonic stem cells","volume":"17","author":"King","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.ymben.2021.04.014_bib37","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/s41467-017-01222-y","article-title":"Drug-tunable multidimensional synthetic gene control using inducible degron-tagged dCas9 effectors","volume":"8","author":"Kleinjan","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymben.2021.04.014_bib38","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1002\/btpr.2594","article-title":"Probing the importance of clonality: single cell subcloning of clonally derived CHO cell lines yields widely diverse clones differing in growth, productivity, and product quality","volume":"34","author":"Ko","year":"2018","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib39","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"A flexible aligner and methylation caller for Bisulfite-Seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ymben.2021.04.014_bib40","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/S0960-9822(03)00432-9","article-title":"Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin","volume":"13","author":"Lehnertz","year":"2003","journal-title":"Curr. Biol. CB"},{"key":"10.1016\/j.ymben.2021.04.014_bib41","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1073\/pnas.1014660108","article-title":"Lysine methyltransferase G9a is required for de novo DNA methylation and the establishment, but not the maintenance, of proviral silencing","volume":"108","author":"Leung","year":"2011","journal-title":"Proc. Natl. Acad. Sci. Unit. States Am."},{"key":"10.1016\/j.ymben.2021.04.014_bib42","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nbt.2624","article-title":"Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome","volume":"31","author":"Lewis","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib43","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1039\/C5MB00627A","article-title":"Genetic analysis of the clonal stability of Chinese hamster ovary cells for recombinant protein production","volume":"12","author":"Li","year":"2015","journal-title":"Mol. Biosyst."},{"key":"10.1016\/j.ymben.2021.04.014_bib44","article-title":"FISH-based analysis of clonally derived CHO cell populations reveals high probability for transgene integration in a terminal region of chromosome 1 (1q13)","volume":"11","author":"Li","year":"2016","journal-title":"PloS One"},{"key":"10.1016\/j.ymben.2021.04.014_bib45","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41467-020-14362-5","article-title":"Interrogation of enhancer function by enhancer-targeting CRISPR epigenetic editing","volume":"11","author":"Li","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymben.2021.04.014_bib46","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0029101","article-title":"Quantification bias caused by plasmid DNA conformation in quantitative real-time PCR assay","volume":"6","author":"Lin","year":"2011","journal-title":"PloS One"},{"key":"10.1016\/j.ymben.2021.04.014_bib47","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/btpr.2038","article-title":"Chinese hamster ovary (CHO) host cell engineering to increase sialylation of recombinant therapeutic proteins by modulating sialyltransferase expression","volume":"31","author":"Lin","year":"2015","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib48","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods San Diego Calif"},{"key":"10.1016\/j.ymben.2021.04.014_bib49","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41467-018-07829-z","article-title":"Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling","volume":"10","author":"Longbotham","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ymben.2021.04.014_bib50","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1093\/nar\/gkx1222","article-title":"Multimode drug inducible CRISPR\/Cas9 devices for transcriptional activation and genome editing","volume":"46","author":"Lu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib51","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/bit.22751","article-title":"Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies","volume":"106","author":"Malphettes","year":"2010","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib52","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1002\/btpr.1919","article-title":"Insertion of core CpG island element into human CMV promoter for enhancing recombinant protein expression stability in CHO cells","volume":"30","author":"Mariati","year":"2014","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib53","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700217","article-title":"CRISPR-based targeted epigenetic editing enables gene expression modulation of the silenced beta-galactoside alpha-2,6-sialyltransferase 1 in CHO cells","volume":"13","author":"Marx","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib54","doi-asserted-by":"crossref","DOI":"10.1038\/srep16952","article-title":"CMV promoter mutants with a reduced propensity to productivity loss in CHO cells","volume":"5","author":"Moritz","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ymben.2021.04.014_bib55","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/btpr.2271","article-title":"High levels of histone H3 acetylation at the CMV promoter are predictive of stable expression in Chinese hamster ovary cells","volume":"32","author":"Moritz","year":"2016","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib56","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/(SICI)1097-0290(19970320)53:6<594::AID-BIT7>3.0.CO;2-H","article-title":"Differential stability of proteolytically active and inactive recombinant metalloproteinase in Chinese hamster ovary cells","volume":"53","author":"Morrison","year":"1997","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib57","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201900125","article-title":"Novel promoters derived from Chinese Hamster Ovary cells via in silico and in vitro analysis","volume":"14","author":"Nguyen","year":"2019","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib58","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1111\/j.1440-1681.2011.05599.x","article-title":"GAPDH: A common enzyme with uncommon functions","volume":"39","author":"Nicholls","year":"2012","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"10.1016\/j.ymben.2021.04.014_bib59","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700231","article-title":"RNA-seq highlights high clonal variation in monoclonal antibody producing CHO cells","volume":"13","author":"Orellana","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib60","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1002\/bit.23216","article-title":"Promoter methylation and transgene copy numbers predict unstable protein production in recombinant Chinese hamster ovary cell lines","volume":"108","author":"Osterlehner","year":"2011","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib61","article-title":"Single copy transgene integration in a transcriptionally active site for recombinant protein synthesis","volume":"13","author":"O\u2019Brien","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib62","article-title":"Ezh2-dCas9 and KRAB-dCas9 enable engineering of epigenetic memory in a context-dependent manner","volume":"12","author":"O'Geen","year":"2019","journal-title":"Epigenet. Chromatin"},{"key":"10.1016\/j.ymben.2021.04.014_bib63","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/btpr.2655","article-title":"Antibody expression stability in CHO clonally derived cell lines and their subclones: role of methylation in phenotypic and epigenetic heterogeneity","volume":"34","author":"Patel","year":"2018","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib64","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1182\/blood-2008-03-144600","article-title":"Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells","volume":"112","author":"Peipp","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.ymben.2021.04.014_bib65","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1080\/19420862.2018.1466767","article-title":"The \u201cless-is-more\u201d in therapeutic antibodies: afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity","volume":"10","author":"Pereira","year":"2018","journal-title":"mAbs"},{"key":"10.1016\/j.ymben.2021.04.014_bib66","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S1097-2765(03)00477-5","article-title":"Partitioning and plasticity of repressive histone methylation states in mammalian chromatin","volume":"12","author":"Peters","year":"2003","journal-title":"Mol. Cell."},{"key":"10.1016\/j.ymben.2021.04.014_bib67","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1124\/jpet.109.155671","article-title":"Glyceraldehyde 3-phosphate dehydrogenase depletion induces cell cycle arrest and resistance to antimetabolites in human carcinoma cell lines","volume":"331","author":"Phadke","year":"2009","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ymben.2021.04.014_bib68","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/bit.22946","article-title":"Selection of CHO host cell subclones with increased specific antibody production rates by repeated cycles of transient transfection and cell sorting","volume":"108","author":"Pichler","year":"2011","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib69","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008432","article-title":"Intraclonal protein expression heterogeneity in recombinant CHO cells","volume":"4","author":"Pilbrough","year":"2009","journal-title":"PloS One"},{"key":"10.1016\/j.ymben.2021.04.014_bib70","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejpb.2009.10.002","article-title":"Guidelines to cell engineering for monoclonal antibody production","volume":"74","author":"Rita Costa","year":"2010","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ymben.2021.04.014_bib71","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/bit.25876","article-title":"Deletion of a telomeric region on chromosome 8 correlates with higher productivity and stability of CHO cell lines","volume":"113","author":"Ritter","year":"2016","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib72","article-title":"Engineered and natural promoters and chromatin-modifying elements for recombinant protein expression in CHO cells","volume":"13","author":"Romanova","year":"2017","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib73","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.bbagrm.2014.02.007","article-title":"Understanding the relationship between DNA methylation and histone lysine methylation","volume":"1839","author":"Rose","year":"2014","journal-title":"Biochim. Biophys. Acta BBA - Gene Regul. Mech."},{"key":"10.1016\/j.ymben.2021.04.014_bib74","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nsmb.2391","article-title":"Association of UHRF1 with H3K9 methylation directs the maintenance of DNA methylation","volume":"19","author":"Rothbart","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.ymben.2021.04.014_bib75","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature08674","article-title":"KAP1 controls endogenous retroviruses in embryonic stem cells","volume":"463","author":"Rowe","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.ymben.2021.04.014_bib76","first-page":"519","article-title":"De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs\/KAP1 and ESET","volume":"140","author":"Rowe","year":"2013","journal-title":"Dev. Camb. Engl."},{"key":"10.1016\/j.ymben.2021.04.014_bib77","doi-asserted-by":"crossref","DOI":"10.1002\/bit.26722","article-title":"A reference genome of the Chinese hamster based on a hybrid assembly strategy","author":"Rupp","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib78","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1756-8935-8-3","article-title":"Constitutive heterochromatin formation and transcription in mammals","volume":"8","author":"Saksouk","year":"2015","journal-title":"Epigenet. Chromatin"},{"key":"10.1016\/j.ymben.2021.04.014_bib79","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700211","article-title":"Enhanced genome editing tools for multi-gene deletion knock-out approaches using paired CRISPR sgRNAs in CHO cells","volume":"13","author":"Schmieder","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib80","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1074\/jbc.M210665200","article-title":"The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity","volume":"278","author":"Shinkawa","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ymben.2021.04.014_bib81","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.jmb.2012.11.038","article-title":"Targeted methylation and gene silencing of VEGF-A in human cells by using a designed dnmt3a\u2013Dnmt3L single-chain fusion protein with increased DNA methylation activity","volume":"425","author":"Siddique","year":"2013","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ymben.2021.04.014_bib82","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0047510","article-title":"Housekeeping gene selection advisory: glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and \u03b2-actin are targets of miR-644a","volume":"7","author":"Sikand","year":"2012","journal-title":"PloS One"},{"key":"10.1016\/j.ymben.2021.04.014_bib83","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jbiotec.2014.12.009","article-title":"Stability of single copy transgene expression in CHOK1 cells is affected by histone modifications but not by DNA methylation","volume":"195","author":"Spencer","year":"2015","journal-title":"J. Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib84","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.jgg.2016.05.008","article-title":"Epigenetic modulations rendering cell-to-cell variability and phenotypic metastability","volume":"43","author":"Spencer","year":"2016","journal-title":"J. Genet. Genomics"},{"key":"10.1016\/j.ymben.2021.04.014_bib85","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0124633","article-title":"CCTop: an intuitive, flexible and reliable CRISPR\/Cas9 target prediction tool","volume":"10","author":"Stemmer","year":"2015","journal-title":"PloS One"},{"key":"10.1016\/j.ymben.2021.04.014_bib86","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1093\/nar\/gkw1112","article-title":"Efficient targeted DNA methylation with chimeric dCas9\u2013Dnmt3a\u2013Dnmt3L methyltransferase","volume":"45","author":"Stepper","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib87","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.2144\/00286ir01","article-title":"The sequence manipulation suite: JavaScript programs for analyzing and formatting protein and DNA sequences","volume":"28","author":"Stothard","year":"2000","journal-title":"Biotechniques"},{"key":"10.1016\/j.ymben.2021.04.014_bib88","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/elsc.201400218","article-title":"Functional knockout of FUT8 in Chinese hamster ovary cells using CRISPR\/Cas9 to produce a defucosylated antibody","volume":"15","author":"Sun","year":"2015","journal-title":"Eng. Life Sci."},{"key":"10.1016\/j.ymben.2021.04.014_bib89","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cell.2014.09.039","article-title":"A protein-tagging system for signal amplification in gene expression and fluorescence imaging","volume":"159","author":"Tanenbaum","year":"2014","journal-title":"Cell"},{"key":"10.1016\/j.ymben.2021.04.014_bib90","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jbiotec.2011.11.014","article-title":"Growth, productivity and protein glycosylation in a CHO EpoFc producer cell line adapted to glutamine-free growth","volume":"157","author":"Taschwer","year":"2012","journal-title":"J. Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib91","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/btpr.2666","article-title":"Characterization of phenotypic and genotypic diversity in subclones derived from a clonal cell line","volume":"34","author":"Tharmalingam","year":"2018","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molcel.2007.09.011","article-title":"Facultative heterochromatin: is there a distinctive molecular signature?","volume":"28","author":"Trojer","year":"2007","journal-title":"Mol. Cell."},{"key":"10.1016\/j.ymben.2021.04.014_bib93","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700495","article-title":"Changes in chromosome counts and patterns in CHO cell lines upon generation of recombinant cell lines and subcloning","volume":"13","author":"Vcelar","year":"2018","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib94","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/nar\/gky947","article-title":"DNMT3L facilitates DNA methylation partly by maintaining DNMT3A stability in mouse embryonic stem cells","volume":"47","author":"Veland","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib95","article-title":"Repurposing the CRISPR-Cas9 system for targeted DNA methylation","volume":"gkw159","author":"Vojta","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib96","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.csbj.2020.05.020","article-title":"Directed evolution approach to enhance efficiency and speed of outgrowth during single cell subcloning of Chinese Hamster Ovary cells","volume":"18","author":"Weinguny","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib97","doi-asserted-by":"crossref","first-page":"3435","DOI":"10.1002\/bit.27493","article-title":"Random epigenetic modulation of CHO cells by repeated knockdown of DNA methyltransferases increases population diversity and enables sorting of cells with higher production capacities","volume":"117","author":"Weinguny","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib113","doi-asserted-by":"crossref","DOI":"10.1002\/biot.202000350","article-title":"Subcloning induces changes in the DNA-methylation pattern of outgrowing Chinese hamster ovary cell colonies","author":"Weinguny","year":"2021","journal-title":"Biotechnology J."},{"key":"10.1016\/j.ymben.2021.04.014_bib98","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1001106","article-title":"DNMT3L modulates significant and distinct flanking sequence preference for DNA methylation by DNMT3A and DNMT3B in vivo","volume":"6","author":"Wienholz","year":"2010","journal-title":"PLoS Genet."},{"key":"10.1016\/j.ymben.2021.04.014_bib99","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3390\/pr5020020","article-title":"Cloning of CHO cells, productivity and genetic stability\u2014a discussion","volume":"5","author":"Wurm","year":"2017","journal-title":"Processes"},{"key":"10.1016\/j.ymben.2021.04.014_bib100","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nrg3035","article-title":"Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation","volume":"12","author":"Wutz","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.ymben.2021.04.014_bib101","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jmb.2011.11.012","article-title":"UHRF1 double tudor domain and the adjacent PHD finger act together to recognize K9me3-containing histone H3 tail","volume":"415","author":"Xie","year":"2012","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ymben.2021.04.014_bib102","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/nbt.1932","article-title":"The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line","volume":"29","author":"Xu","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymben.2021.04.014_bib103","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jbiosc.2016.01.002","article-title":"Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells","volume":"122","author":"Yamano","year":"2016","journal-title":"J. Biosci. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib104","doi-asserted-by":"crossref","DOI":"10.1002\/biot.201700175","article-title":"Optimized selection marker and CHO host cell combinations for generating high monoclonal antibody producing cell lines","volume":"12","author":"Yeo","year":"2017","journal-title":"Biotechnol. J."},{"key":"10.1016\/j.ymben.2021.04.014_bib105","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41592-018-0048-5","article-title":"An enhanced CRISPR repressor for targeted mammalian gene regulation","volume":"15","author":"Yeo","year":"2018","journal-title":"Nat. Methods"},{"key":"10.1016\/j.ymben.2021.04.014_bib106","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1002\/bit.25650","article-title":"Glycoengineering of Chinese hamster ovary cells for enhanced erythropoietin N-glycan branching and sialylation","volume":"112","author":"Yin","year":"2015","journal-title":"Biotechnol. Bioeng."},{"key":"10.1016\/j.ymben.2021.04.014_bib107","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1021\/bp000114e","article-title":"Amplified gene location in chromosomal DNA affected recombinant protein production and stability of amplified genes","volume":"16","author":"Yoshikawa","year":"2000","journal-title":"Biotechnol. Prog."},{"key":"10.1016\/j.ymben.2021.04.014_bib108","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cell.2014.11.052","article-title":"Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds","volume":"160","author":"Zalatan","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymben.2021.04.014_bib109","doi-asserted-by":"crossref","first-page":"D754","DOI":"10.1093\/nar\/gkx1098","article-title":"Ensembl","volume":"46","author":"Zerbino","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymben.2021.04.014_bib110","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","article-title":"Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-cas system","volume":"163","author":"Zetsche","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.ymben.2021.04.014_bib111","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.15252\/embr.201540945","article-title":"The interplay of histone modifications \u2013 writers that read","volume":"16","author":"Zhang","year":"2015","journal-title":"EMBO Rep."},{"key":"10.1016\/j.ymben.2021.04.014_bib112","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature25477","article-title":"Structural basis for DNMT3A-mediated de novo DNA methylation","volume":"554","author":"Zhang","year":"2018","journal-title":"Nature"}],"container-title":["Metabolic Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717621000756?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1096717621000756?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T23:10:31Z","timestamp":1761088231000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1096717621000756"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":113,"alternative-id":["S1096717621000756"],"URL":"https:\/\/doi.org\/10.1016\/j.ymben.2021.04.014","relation":{},"ISSN":["1096-7176"],"issn-type":[{"value":"1096-7176","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Enhanced targeted DNA methylation of the CMV and endogenous promoters with dCas9-DNMT3A3L entails distinct subsequent histone modification changes in CHO cells","name":"articletitle","label":"Article Title"},{"value":"Metabolic Engineering","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymben.2021.04.014","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc. on behalf of International Metabolic Engineering Society.","name":"copyright","label":"Copyright"}]}}