title: Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time.
abstract: 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. Biotechnol. Bioeng. 2016;113: 2241-2253. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.|Graz University of Technology, Graz, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Feichtinger
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Hernández
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.|Graz University of Technology, Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanscho
authors.affiliation: University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, 1190, Austria.
authors.forename: Norbert
authors.initials: N
authors.lastname: Auer
authors.affiliation: University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, 1190, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hackl
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Jadhav
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.|Graz University of Technology, Graz, Austria.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Krempl
authors.affiliation: CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Schmidl
authors.affiliation: CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Farlik
authors.affiliation: CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schuster
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Angelika
authors.initials: A
authors.lastname: Merkel
authors.affiliation: Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sommer
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.affiliation: Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.affiliation: CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bock
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria.|Graz University of Technology, Graz, Austria.
authors.forename: Gerhard G
authors.initials: GG
authors.lastname: Thallinger
authors.affiliation: Austrian Center of Industrial Biotechnology, Muthgasse 11, Vienna, 1190, Austria. nicole.borth@boku.ac.at.|University of Natural Resources and Life Sciences Vienna, Muthgasse 18, Vienna, 1190, Austria. nicole.borth@boku.ac.at.
authors.forename: Nicole
authors.initials: N
authors.lastname: Borth
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D016466:CHO Cells / Q000145:classification* / Q000502:physiology*; D003412:Cricetulus; D044127:Epigenesis, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics; D016678:Genome / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics*; D013997:Time Factors
keywords: Chinese hamster ovary cells; DNA-methylation; epigenome; genome variation; histone modifications