Institute of Cell Culture Technology, Bielefeld University, Bielefeld, Germany; Center for Biotechnology, Bielefeld University, Bielefeld, Germany.
Institute of Cell Culture Technology, Bielefeld University, Bielefeld, Germany; Center for Biotechnology, Bielefeld University, Bielefeld, Germany.
J Biotechnol. 2017 Sep 20;258:206-210. doi: 10.1016/j.jbiotec.2017.08.005. Epub 2017 Aug 8.
Chinese hamster ovary (CHO) cells account for the production of the majority of biopharmaceutical molecules - however, the molecular basis for their versatile properties is not entirely understood yet and the underlying cellular processes need to be characterized in detail. One such process that is supposed to contribute significantly to CHO cell phenotype is methylation of DNA at cytosine residues. DNA methylation was shown to be involved in several central biological processes in humans and to contribute to diseases like cancer. Early studies of DNA methylation in CHO mostly focused on methylation of single recombinant genes and promoters and proved a correlation between DNA methylation status and recombinant gene expression or production stability. More recent publications utilized the CHO genomic and transcriptomic data available since 2011 and provided first insights into the CHO DNA methylation landscape and DNA methylation changes in response to effector molecules or culture conditions. Generally, further genome-wide studies of DNA methylation in CHO will be required to shed light on the relevance of this process regarding biopharmaceuticals production and might, e.g., address a potential link between CHO cell metabolism and DNA methylation or provide novel targets for rational cell line engineering.
中国仓鼠卵巢（CHO）细胞是大多数生物制药分子的生产来源——然而，其多功能特性的分子基础尚未完全了解，需要详细描述相关的细胞过程。在这些过程中，有一种过程被认为对 CHO 细胞表型有重要贡献，那就是胞嘧啶残基的 DNA 甲基化。在人类中，DNA 甲基化被证明参与了几个中心的生物学过程，并导致了癌症等疾病的发生。CHO 中 DNA 甲基化的早期研究主要集中在单个重组基因和启动子的甲基化上，并证明了 DNA 甲基化状态与重组基因表达或生产稳定性之间存在相关性。最近的出版物利用了 2011 年以来可用的 CHO 基因组和转录组数据，首次深入了解了 CHO 的 DNA 甲基化景观以及对效应分子或培养条件的响应中的 DNA 甲基化变化。通常，需要进一步进行 CHO 中 DNA 甲基化的全基因组研究，以阐明该过程在生物制药生产方面的相关性，例如，解决 CHO 细胞代谢与 DNA 甲基化之间的潜在联系，或为合理的细胞系工程提供新的靶点。
