title: Integrative analysis of DNA methylation and gene expression in butyrate-treated CHO cells.
abstract: The cellular mechanisms responsible for the versatile properties of CHO cells as the major production cell line for biopharmaceutical molecules are not entirely understood yet, although several 'omics' data facilitate the understanding of CHO cells and their reactions to environmental conditions. However, genome-wide studies of epigenetic processes such as DNA methylation are still limited. To prove the applicability and usefulness of integrating DNA methylation and gene expression data in a biotechnological context, we exemplarily analyzed the time course of cellular reactions upon butyrate addition in antibody-producing CHO cells by whole-genome bisulfite sequencing and CHO-specific cDNA microarrays. Gene expression and DNA methylation analyses showed that pathways known to be affected by butyrate, including cell cycle and apoptosis, as well as pathways potentially involved in butyrate-induced hyperproductivity such as central energy metabolism and protein biosynthesis were affected. Differentially methylated regions were furthermore found to contain binding-site motifs of specific transcription factors and were hypothesized to represent regulatory regions closely connected to the cellular response to butyrate. Generally, our experiment underlines the benefit of integrating DNA methylation and gene expression data, as it provided potential novel candidate genes for rational cell line development and allowed for new insights into the butyrate effect on CHO cells.
authors.affiliation: Institute of Cell Culture Technology, Bielefeld University, Bielefeld, Germany; Center for Biotechnology, Bielefeld University, Bielefeld, Germany. Electronic address: anna.wippermann@uni-bielefeld.de.
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: Department of Biorescources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Gießen, 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Noll
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D016466:CHO Cells / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003412:Cricetulus; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015870:Gene Expression; D020869:Gene Expression Profiling; D063990:Gene Ontology; D016678:Genome; D008969:Molecular Sequence Data; D011506:Proteins / Q000378:metabolism; D014157:Transcription Factors; D000073336:Whole Genome Sequencing
chemical_list: D002087:Butyrates; D011506:Proteins; D014157:Transcription Factors
keywords: Butyrate; CHO; DNA methylation sequencing; Data integration; Epigenetics; Gene expression