Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter
Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation...
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| Veröffentlicht in: | Molecular biotechnology 2017-08, Vol.59 (8), p.315-322 |
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| creator | Soo, Benjamin P. C. Tay, Julian Ng, Shirelle Ho, Steven C. L. Yang, Yuansheng Chao, Sheng-Hao |
| description | Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines. |
| doi_str_mv | 10.1007/s12033-017-0019-6 |
| format | Article |
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C. ; Tay, Julian ; Ng, Shirelle ; Ho, Steven C. L. ; Yang, Yuansheng ; Chao, Sheng-Hao</creator><creatorcontrib>Soo, Benjamin P. C. ; Tay, Julian ; Ng, Shirelle ; Ho, Steven C. L. ; Yang, Yuansheng ; Chao, Sheng-Hao</creatorcontrib><description>Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.</description><identifier>ISSN: 1073-6085</identifier><identifier>EISSN: 1559-0305</identifier><identifier>DOI: 10.1007/s12033-017-0019-6</identifier><identifier>PMID: 28664508</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Abundance ; Acetylation ; Animals ; Biochemistry ; Biological Techniques ; Biotechnology ; Cell Biology ; Cell lines ; Chemistry ; Chemistry and Materials Science ; CHO Cells ; Chromatin ; Cloning ; Correlation ; Correlation analysis ; Cricetinae ; Cricetulus ; Cytomegalovirus ; Cytomegalovirus - genetics ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Enhancer Elements, Genetic ; Epigenetics ; Gene Dosage ; Gene expression ; Genes, Immediate-Early ; Histones - metabolism ; Human Genetics ; Humans ; Immunotherapy ; Lysine ; Lysine - metabolism ; Mammalian cells ; Mammals ; Markers ; Methylation ; Monoclonal antibodies ; Original Paper ; Promoter Regions, Genetic ; Protein Science ; Proteins ; Recombinant Proteins - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Studies ; Transcription ; Trastuzumab ; Trastuzumab - biosynthesis ; Trastuzumab - genetics ; Trastuzumab - metabolism</subject><ispartof>Molecular biotechnology, 2017-08, Vol.59 (8), p.315-322</ispartof><rights>Springer Science+Business Media, LLC 2017</rights><rights>Molecular Biotechnology is a copyright of Springer, 2017.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-39cb008586845c404f2ed87c3c5912131f1b1da40d1e8df3092e2ff23db8b1c73</citedby><cites>FETCH-LOGICAL-c372t-39cb008586845c404f2ed87c3c5912131f1b1da40d1e8df3092e2ff23db8b1c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12033-017-0019-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12033-017-0019-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28664508$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soo, Benjamin P. C.</creatorcontrib><creatorcontrib>Tay, Julian</creatorcontrib><creatorcontrib>Ng, Shirelle</creatorcontrib><creatorcontrib>Ho, Steven C. L.</creatorcontrib><creatorcontrib>Yang, Yuansheng</creatorcontrib><creatorcontrib>Chao, Sheng-Hao</creatorcontrib><title>Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter</title><title>Molecular biotechnology</title><addtitle>Mol Biotechnol</addtitle><addtitle>Mol Biotechnol</addtitle><description>Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.</description><subject>Abundance</subject><subject>Acetylation</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biological Techniques</subject><subject>Biotechnology</subject><subject>Cell Biology</subject><subject>Cell lines</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>CHO Cells</subject><subject>Chromatin</subject><subject>Cloning</subject><subject>Correlation</subject><subject>Correlation analysis</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Enhancer Elements, Genetic</subject><subject>Epigenetics</subject><subject>Gene Dosage</subject><subject>Gene expression</subject><subject>Genes, Immediate-Early</subject><subject>Histones - metabolism</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Lysine</subject><subject>Lysine - metabolism</subject><subject>Mammalian cells</subject><subject>Mammals</subject><subject>Markers</subject><subject>Methylation</subject><subject>Monoclonal antibodies</subject><subject>Original Paper</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Science</subject><subject>Proteins</subject><subject>Recombinant Proteins - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Studies</subject><subject>Transcription</subject><subject>Trastuzumab</subject><subject>Trastuzumab - biosynthesis</subject><subject>Trastuzumab - genetics</subject><subject>Trastuzumab - metabolism</subject><issn>1073-6085</issn><issn>1559-0305</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kc9u1DAQxiMEoqXwAFyQJS5cDON_iXMsq4VWtAIhOFuOM2mzSuzFdoB9El4Xhy0IIXGy5fl934znq6qnDF4ygOZVYhyEoMAaCsBaWt-rTplSLQUB6n65QyNoDVqdVI9S2gFwpqR4WJ1wXddSgT6tfmxCjDjZPAZPXmP-hujJ9vs-YkrrUxjIR3Rh7kZvfSYfYsg4-kSs78l5t_jeeocrdSHeyWsUpGjyLZKtv10r8Vdpma0nm0MOM97YKXwd45LItd2FSC7nGfvRZqRbG6fD2mAuLeLj6sFgp4RP7s6z6vOb7afNBb16__Zyc35FnWh4pqJ1HZQP6lpL5STIgWOvGyecahlngg2sY72V0DPU_SCg5ciHgYu-0x1zjTirXhx99zF8WTBlM4_J4TRZj2FJhrVMCamUVAV9_g-6C0v0ZbpCcYCy2lYXih0pF0NKEQezj-Ns48EwMGtq5piaKamZNTVTF82zO-elK-v4o_gdUwH4EUil5G8w_tX6v64_Ad4Zoqc</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Soo, Benjamin P. 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C.</au><au>Tay, Julian</au><au>Ng, Shirelle</au><au>Ho, Steven C. L.</au><au>Yang, Yuansheng</au><au>Chao, Sheng-Hao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter</atitle><jtitle>Molecular biotechnology</jtitle><stitle>Mol Biotechnol</stitle><addtitle>Mol Biotechnol</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>59</volume><issue>8</issue><spage>315</spage><epage>322</epage><pages>315-322</pages><issn>1073-6085</issn><eissn>1559-0305</eissn><abstract>Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>28664508</pmid><doi>10.1007/s12033-017-0019-6</doi><tpages>8</tpages></addata></record> |
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| subjects | Abundance Acetylation Animals Biochemistry Biological Techniques Biotechnology Cell Biology Cell lines Chemistry Chemistry and Materials Science CHO Cells Chromatin Cloning Correlation Correlation analysis Cricetinae Cricetulus Cytomegalovirus Cytomegalovirus - genetics Deoxyribonucleic acid DNA DNA Methylation Enhancer Elements, Genetic Epigenetics Gene Dosage Gene expression Genes, Immediate-Early Histones - metabolism Human Genetics Humans Immunotherapy Lysine Lysine - metabolism Mammalian cells Mammals Markers Methylation Monoclonal antibodies Original Paper Promoter Regions, Genetic Protein Science Proteins Recombinant Proteins - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Studies Transcription Trastuzumab Trastuzumab - biosynthesis Trastuzumab - genetics Trastuzumab - metabolism |
| title | Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter |
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