Comprehensive Mapping of Functional Enhancers in Chinese Hamster Ovary Cells

In this publication by Biotechnology & Bioengineering, (DOI:10.1002/bit.70076) the authors present a genome-wide characterization of enhancer elements in CHO cells — the workhorse mammalian platform for biopharmaceutical production. Using STARR-seq (Self-Transcribing Active Regulatory Region sequencing), the team systematically measured enhancer activity across the CHO genome and integrated these data with chromatin accessibility (ATAC-seq) and histone modification profiles. They discovered thousands of novel regulatory regions, some of which were as strong as established viral enhancers in driving expression. A key insight is that many enhancers are “inaccessible” in their native chromatin environment, suggesting potential for synthetic activation or repositioning. The study also uses deep learning to identify motif signatures—specifically ETS and YY1 transcription factor binding patterns—that are predictive of enhancer strength. Experimental disruption of YY1 motifs confirmed their functional importance, underscoring YY1 as a critical activator in CHO cells. Overall, this work provides the first functional enhancer atlas in CHO cells and lays a foundation for rational engineering of transcriptional regulation to optimize transgene expression in biomanufacturing settings.