title: The DNA methylation landscape of Chinese hamster ovary (CHO) DP-12 cells.
abstract: Chinese hamster ovary (CHO) cells represent the most commonly used production cell line for therapeutic proteins. By recent genome and transcriptome sequencing a basis was created for future investigations of genotype-phenotype relationships and for improvement of CHO cell productivity and product quality. In this context information is missing about DNA cytosine methylation as a crucial epigenetic modification and an important element in mammalian genome regulation and development. Here, we present the first DNA methylation map of a CHO cell line in single-base resolution that was generated by whole genome bisulfite sequencing combined with gene expression analysis by CHO microarrays. We show CHO DP-12 cells to exhibit global hypomethylation compared to a majority of mammalian methylomes and hypermethylation of CpG-dense regions at gene promoters called CpG islands. We also observed partially methylated domains that cover 62% of the CHO DP-12 cell genome and contain functional clusters of genes. Gene expression analysis showed these clusters to be either highly or weakly expressed with regard to CHO-specific characteristics and hence proves DNA methylation in CHO cells to be an important link between genomics and transcriptomics.
authors.affiliation: Institute of Cell Culture Technology, Bielefeld University, Bielefeld, Germany; Center for Biotechnology, Bielefeld University, Bielefeld, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Wippermann
authors.affiliation: Bioinformatics and Systems Biology, Justus-Liebig-University, Giessen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Rupp
authors.affiliation: Center for Biotechnology, Bielefeld University, Bielefeld, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Brinkrolf
authors.affiliation: Institute of Cell Culture Technology, Bielefeld University, Bielefeld, Germany; Center for Biotechnology, Bielefeld University, Bielefeld, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Hoffrogge
authors.affiliation: Institute of Cell Culture Technology, Bielefeld University, Bielefeld, Germany; Center for Biotechnology, Bielefeld University, Bielefeld, Germany. Electronic address: thomas.noll@uni-bielefeld.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Noll
mesh_terms: D000818:Animals; D016466:CHO Cells; D018899:CpG Islands / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics
keywords: CHO; DNA methylation; Epigenetics; Gene expression; Whole genome bisulfite sequencing