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Pioneer Factor FOXA1 Boosts CHO Cell Productivity.

Sienna P Butterfield1, Fay L Saunders2, Robert J White1

  • 1Department of Biology, University of York, York, UK.

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|January 9, 2026
PubMed
Summary
This summary is machine-generated.

Overexpressing forkhead box A1 (FOXA1) enhances biologics production by improving transgene accessibility in Chinese hamster ovary (CHO) cells. This strategy boosts monoclonal antibody yield and cell viability for biomanufacturing.

Keywords:
CHOEF1αFOXA1epigeneticsmAbpioneer factor

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Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cell Biology

Background:

  • Industrial biologics production relies on transgenes in host cells like Chinese hamster ovary (CHO) cells.
  • Epigenetic silencing via heterochromatin spread reduces transgene promoter accessibility and productivity.
  • Pioneer factors, such as forkhead box A1 (FOXA1), can counteract heterochromatin and enhance gene transcription.

Purpose of the Study:

  • To investigate the role of FOXA1 in regulating transgene promoter accessibility and productivity in CHO cells.
  • To determine if FOXA1 overexpression can enhance monoclonal antibody production in industrial cell lines.
  • To elucidate the mechanisms by which FOXA1 influences transcription and cell viability.

Main Methods:

  • Overexpression of FOXA1 in CHO-K1 and CHO-DG44 cell lines.
  • Assessment of FOXA1 binding to commonly used EF1α and CMV promoters.
  • Quantification of monoclonal antibody production.
  • Analysis of epigenetic modifier recruitment and chromatin remodeling.
  • Evaluation of endogenous gene expression related to cell viability.

Main Results:

  • FOXA1 binds to EF1α and CMV promoters, increasing their accessibility.
  • Overexpression of FOXA1 significantly enhanced monoclonal antibody production in CHO cells.
  • FOXA1 recruits epigenetic modifiers and chromatin remodeling complexes to optimize transcription.
  • FOXA1 overexpression induced endogenous genes, improving cell viability.

Conclusions:

  • FOXA1 acts as a pioneer factor to enhance transgene expression and productivity in CHO cells.
  • FOXA1-mediated reprogramming of promoter epigenetics offers a strategy to boost biomanufacturing yields.
  • This approach improves both cell-specific productivity and cell viability, demonstrating significant biomanufacturing potential.