Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time.
Comprehensive genome and epigenome characterization of CHO cells in response to evolutionary pressures and over time.
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DOI：
10.1002/bit.25990
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发表时间：
2016-10
影响因子：
3.8
通讯作者：
Borth, Nicole
中科院分区：
文献类型：
--
作者：
Feichtinger, Julia;Hernandez, Inmaculada;Fischer, Christoph;Hanscho, Michael;Auer, Norbert;Hackl, Matthias;Jadhav, Vaibhav;Baumann, Martina;Krempl, Peter M.;Schmidl, Christian;Farlik, Matthias;Schuster, Michael;Merkel, Angelika;Sommer, Andreas;Heath, Simon;Rico, Daniel;Bock, Christoph;Thallinger, Gerhard G.;Borth, Nicole
CHO 细胞最显着的特征是其适应性，能够高效生产蛋白质以及在各种培养条件下生长，但也会导致基因组和表型不稳定。为了研究基因组和表观遗传修饰对表型进化的相对贡献，提供了六种相关 CHO 细胞系的全面基因组和表观基因组数据，包括对扰动（不同的培养条件和培养基以及选择具有增加的瞬时生产力的特定表型）和稳态（在恒定条件下延长培养时间）的反应。每次扰动时，DNA 甲基化模式都会发生明显的转变，而在恒定条件下，随着时间的推移，几乎没有发生任何变化。在指数生长期和稳定生长期之间仅观察到微小的 DNA 甲基化变化；然而，在整个分批培养过程中，组蛋白修饰模式经历了持续的适应。六种细胞系之间的基因组序列在 SNP、InDels 和结构变异水平上的变异很大，无论是在扰动还是在恒定条件下随时间变化。这里提出的综合资源可能为基于表观遗传机制的工业生物过程中改进基因表达的控制和操作打开大门。生物技术。生物工程。 2016；113：2241–2253。 © 2016 作者。生物技术和生物工程由 Wiley periodicals, Inc. 出版
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.
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