Epigenomic features revealed by ATAC‐seq impact transgene expression in CHO cells

• DOI: 10.1002/bit.27701
• Publication Date: 2021-02-01T03:33:59Z
• Authors: Zion Lee; Marina Raabe; Wei‐Shou Hu
• Keywords: Epigenomics

Different regions of a mammalian genome have different accessibilities to transcriptional machinery. The integration site transgene affects how actively it is transcribed. Highly accessible genomic called super-enhancers been recently described as strong regulatory elements that shape cell identity. Super-enhancers identified in Chinese hamster ovary (CHO) cells using the Assay for Transposase-Accessible Chromatin Sequencing (ATAC-seq). Genes near super-enhancer had high transcript levels and were enriched oncogenic signaling proliferation functions, consistent with an immortalized phenotype. Inaccessible low ATAC signal also activity. inaccessible remote tissue functions such taste, smell, neuronal activation. A lentiviral reporter assay showed into conferred higher expression than insertion regions. Targeted IgG vector Plec region yielded clones expressed immunoglobulin light chain gene mostly top 20% all transcripts majority 5%. results suggest epigenomic landscape CHO can guide selection sites development lines therapeutic protein production.