DNA methylation contributes to loss in productivity of monoclonal antibody-producing CHO cell lines

Journal of Biotechnology

Volumn 147, Issue 3-4, 2010, Pages 180-185

  Yang, Yuansheng ^a   Mariati, ^a   Chusainow, Janet ^b   Yap, Miranda G S ^a,c  

^a AGENCY FOR SCIENCE   (Singapore)

^b MAX PLANCK INSTITUTE OF MOLECULAR CELL BIOLOGY AND GENETICS   (Germany)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

CHO cells; DNA methylation; Gene silencing; Monoclonal antibody; Stability

Indexed keywords

CELL LINES; CHINESE HAMSTER OVARY; CHO CELL; DEMETHYLATION; DNA METHYLATION; GENE SILENCING; HEAVY CHAIN; HUMAN CYTOMEGALOVIRUS; INDUSTRIAL PRODUCTION; LIGHT CHAIN; MAMMALIAN CELLS; MOLECULAR ANALYSIS; MRNA LEVEL; QUANTITATIVE REAL TIME PCR; RECOMBINANT MONOCLONAL ANTIBODY; THERAPEUTIC PROTEIN;

ALKYLATION; CELL CULTURE; CONVERGENCE OF NUMERICAL METHODS; GENETIC ENGINEERING; MONOCLONAL ANTIBODIES; PRODUCTIVITY; PROTEINS; TRANSCRIPTION;

POLYMERASE CHAIN REACTION;

5 AZA 2' DEOXYCYTIDINE; MESSENGER RNA; MONOCLONAL ANTIBODY; AZACITIDINE; GAMMA INTERFERON; TRANSACTIVATOR PROTEIN;

ANIMAL TISSUE; ARTICLE; CELL DEATH; CELL GROWTH; CHO CELL; CONTROLLED STUDY; CORRELATION ANALYSIS; CPG ISLAND; DNA METHYLATION; GENE DOSAGE; GENE SILENCING; GENETIC TRANSCRIPTION; HEAVY CHAIN; HUMAN CYTOMEGALOVIRUS; LIGHT CHAIN; NONHUMAN; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PRODUCTIVITY; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; ANIMAL; BIOSYNTHESIS; CRICETULUS; CYTOMEGALOVIRUS; DRUG EFFECT; GENE VECTOR; GENETICS; HAMSTER; HUMAN; IMMEDIATE EARLY GENE; METABOLISM; PROMOTER REGION;

CRICETULUS GRISEUS; HUMAN HERPESVIRUS 5; MAMMALIA;

ANIMALS; ANTIBODIES, MONOCLONAL; AZACITIDINE; CHO CELLS; CRICETINAE; CRICETULUS; CYTOMEGALOVIRUS; DNA METHYLATION; GENES, IMMEDIATE-EARLY; GENETIC VECTORS; HUMANS; INTERFERON-GAMMA; PROMOTER REGIONS, GENETIC; TRANS-ACTIVATORS; TRANSCRIPTION, GENETIC;

EID: 78349303475     PISSN: 01681656     EISSN: 18734863     Source Type: Journal    
DOI: 10.1016/j.jbiotec.2010.04.004     Document Type: Article

References (29)

1. Barnes L.M., Bentley C.M., Dickson A.J. Characterization of the stability of recombinant protein production in the GS-NS0 expression system. Biotechnol. Bioeng. 2001, 73:261-270.
2. Barnes L.M., Bentley C.M., Dickson A.J. Stability of protein production from recombinant mammalian cells. Biotechnol. Bioeng. 2003, 81:631-639.
3. Barnes L.M., Bentley C.M., Dickson A.J. Molecular definition of predictive indicators of stable protein expression in recombinant NSO myeloma cells. Biotechnol. Bioeng. 2004, 85:115-121.
4. Bird A. Perceptions of epigenetics. Nature 2007, 447:396-398.
5. Chiurazzi P., Pomponi M.G., Pietrobono R., Bakker C.E., Neri G., Oostra B.A. Synergistic effect of histone hyperacetylation and DNA demethylation in the reactivation of the FMR1 gene. Hum. Mol. Genet. 1999, 8:2317-2323.
6. Chusainow J., Yang Y.S., Yeo Y.H.M., Toh P.C., Asvadi P., Wong N.S.C., Yap M.G.S. A Study of monoclonal antibody-producing CHO cell lines: what makes a stable high producer?. Biotechnol. Bioeng. 2009, 102:1182-1196.
7. Dang Q., Auten J., Plavec I. Human beta interferon scaffold attachment region inhibits de novo methylation and confers long-term, copy number-dependent expression to a retroviral vector. J. Virol. 2000, 74:2671-2678.
8. Derouazi M., Martinet D., Schmutz N.B., Flaction R., Wicht M., Bertschinger M., Hacker D.L., Beckmann J.S., Wurm F.M. Genetic characterization of CHO production host DG44 and derivative recombinant cell lines. Biochem. Biophys. Res. Commun. 2006, 340:1069-1077.
9. Fann C.H., Guirgis F., Chen G., Lao M.S., Piret J.M. Limitations to the amplification and stability of human tissue-type plasminogen activator expression by Chinese hamster ovary cells. Biotechnol. Bioeng. 2000, 69:204-212.
10. Hejnar J., Hajkova P., Plachy J., Elleder D., Stepanets V., Svoboda J. CPG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression. Proc. Natl. Acad. Sci. USA 2001, 98:565-569.
11. Hong K., Sherley J., Lauffenburger D.A. Methylation of episomal plasmids as a barrier to transient gene expression via a synthetic delivery vector. Biomol. Eng. 2001, 18:185-192.
12. Hsieh J., Fire A. Recognition and silencing of repeated DNA. Annu. Rev. Genet. 2000, 34:187-204.
13. Jun S.C., Kim M.S., Hong H.J., Lee G.M. Limitations to the development of humanized antibody producing Chinese hamster ovary cells using glutamine synthetase-mediated gene amplification. Biotechnol. Prog. 2006, 22:770-780.
14. Kim N.S., Kim S.J., Lee G.M. Clonal variability within dihydrofolate reductase-mediated gene amplified Chinese hamster ovary cells: stability in the absence of selective pressure. Biotechnol. Bioeng. 1998, 60:679-688.
15. Kim S.J., Lee G.M. Cytogenetic analysis of chimeric antibody-producing CHO cells in the course of dihydrofolate reductase-mediated gene amplification and their stability in the absence of selective pressure. Biotechnol. Bioeng. 1999, 64:741-749.
16. Klose R.J., Bird A.P. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 2006, 31:89-97.
17. Lee Y.Y., Wong K.T.K., Nissom P.M., Wong D.C.F., Yap M.G.S. Transcriptional profiling of batch and fed-batch protein-free 293-HEK cultures. Metab. Eng. 2007, 9:52-67.
18. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method. Methods 2001, 25:402-408.
19. McBurney M.W., Mai T., Yang X.F., Jardine K. Evidence for repeat-induced gene silencing in cultured mammalian cells: inactivation of tandem repeats of transfected genes. Exp. Cell Res. 2002, 274:1-8.
20. McGarvey K.M., Fahrner J.A., Greene E., Martens J., Jenuwein T., Baylin S.B. Silenced tumor suppressor genes reactivated by DNA demethylation do not return to a fully euchromatic chromatin state. Cancer Res. 2006, 66:3541-3549.
21. Miranda T.B., Jones P.A. DNA methylation: the nuts and bolts of repression. J. Cell. Physiol. 2007, 213:384-390.
22. Newell-Price J., Clark A.J.L., King P. DNA methylation and silencing of gene expression. Trends Endocrinol. Metab. 2000, 11:142-148.
23. Pikaart M.I., Recillas-Targa F., Felsenfeld G. Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators. Genes Dev. 1998, 12:2852-2862.
24. Prokhortchouk E., Defossez P.A. The cell biology of DNA methylation in mammals. Biochim. Biophys. Acta-Mol. Cell Res. 2008, 1783:2167-2173.
25. Ptashne M. On the use of the word 'epigenetic'. Curr. Biol. 2007, 17:R233-R236.
26. Richards E.J., Elgin S.C.R. Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 2002, 108:489-500.
27. Strutzenberger K., Borth N., Kunert R., Steinfellner W., Katinger H. Changes during subclone development and ageing of human antibody-producing recombinant CHO cells. J. Biotechnol. 1999, 69:215-226.
28. Swindle C.S., Kim H.G., Klug C.A. Mutation of CpGs in the murine stem cell virus retroviral vector long terminal repeat represses silencing in embryonic stem cells. J. Biol. Chem. 2004, 279:34-41.
29. Wurm F.M. Production of recombinant protein therapeutics in cultivated mammalian cells. Nat. Biotechnol. 2004, 22:1393-1398.