Comprehensive Genome and Epigenome Characterization of CHO Cells in Response to Evolutionary Pressures and Over Time

被引：111

作者：

Feichtinger, Julia ^{[1
,2
]}

Hernandez, Inmaculada ^{[1
]}

Fischer, Christoph ^{[1
,2
]}

Hanscho, Michael ^{[1
]}

Auer, Norbert ^{[3
]}

Hackl, Matthias ^{[3
]}

Jadhav, Vaibhav ^{[1
]}

Baumann, Martina ^{[1
]}

Krempl, Peter M. ^{[1
,2
]}

Schmidl, Christian ^{[4
]}

Farlik, Matthias ^{[4
]}

Schuster, Michael ^{[4
]}

Merkel, Angelika ^{[5
]}

Sommer, Andreas ^{[6
]}

Heath, Simon ^{[5
]}

Rico, Daniel ^{[7
]}

Bock, Christoph ^{[4
]}

Thallinger, Gerhard G. ^{[1
,2
]}

Borth, Nicole ^{[1
,3
]}

机构：

[1] Austrian Ctr Ind Biotechnol, Muthgasse 11, A-1190 Vienna, Austria

[2] Graz Univ Technol, Graz, Austria

[3] Univ Nat Resources & Life Sci Vienna, Muthgasse 18, A-1190 Vienna, Austria

[4] Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria

[5] Ctr Genom Regulat CRG, Barcelona, Spain

[6] Res Inst Mol Pathol, Vienna, Austria

[7] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain

来源：

BIOTECHNOLOGY AND BIOENGINEERING | 2016年 / 113卷 / 10期

关键词：

Chinese hamster ovary cells; epigenome; genome variation; DNA-methylation; histone modifications; WIDE DNA METHYLATION; GENE-EXPRESSION; PROTEIN-PRODUCTION; READ ALIGNMENT; STABILITY; TRANSCRIPTOME; PRODUCTIVITY; MICROARRAY; BIOLOGY; LINES;

D O I：

10.1002/bit.25990

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The most striking characteristic of CHO cells is their adaptability, which enables efficient production of proteins as well as growth under a variety of culture conditions, but also results in genomic and phenotypic instability. To investigate the relative contribution of genomic and epigenetic modifications towards phenotype evolution, comprehensive genome and epigenome data are presented for six related CHO cell lines, both in response to perturbations (different culture conditions and media as well as selection of a specific phenotype with increased transient productivity) and in steady state (prolonged time in culture under constant conditions). Clear transitions were observed in DNA-methylation patterns upon each perturbation, while few changes occurred over time under constant conditions. Only minor DNA-methylation changes were observed between exponential and stationary growth phase; however, throughout a batch culture the histone modification pattern underwent continuous adaptation. Variation in genome sequence between the six cell lines on the level of SNPs, InDels, and structural variants is high, both upon perturbation and under constant conditions over time. The here presented comprehensive resource may open the door to improved control and manipulation of gene expression during industrial bioprocesses based on epigenetic mechanisms. (C) 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

引用

页码：2241 / 2253

页数：13

共 67 条

[1]

Akalin A, 2012, GENOME BIOL, V13, DOI [10.1186/gb-2012-13-10-R87, 10.1186/gb-2012-13-10-r87]

[2] Determination of Chinese hamster ovary cell line stability and recombinant antibody expression during long-term culture [J].