Sodium butyrate stimulates monoclonal antibody over-expression in CHO cells by improving gene accessibility
Abstract
Sodium butyrate treatment can increase the specific productivity of recombinant proteins in mammalian cells; however, it dramatically decreases cell growth and frequently leads to apoptosis. We have studied the responses of several Chinese hamster ovary (CHO) cells lines with different specific productivities (qP) to sodium butyrate treatment. Cell clones with lower productivities exhibited greater enhancement from butyrate treatment than cells with higher productivities. As we observed previously in cell clone characterization (Jiang et al., 2006. Biotechnol Prog 22: 313–318), heavy chain (HC) mRNA levels correlate very well with specific productivity and are amplified by butyrate treatment, indicating that sodium butyrate regulates the HC transcription. Sodium butyrate is an inhibitor of histone deacetylation, and possibly, increases gene transcription by enhancing gene accessibility to transcription factors. In this study, we applied DNase I footprinting to probe the HC and LC gene accessibility. We determined that more HC and LC gene copies are accessible by DNase I in sodium butyrate‐treated CHO cells than in untreated controls, demonstrating that sodium butyrate regulates gene transcription by improving gene accessibility. However, the increase in accessibility did not correlate with the increase in transcript abundance, suggesting that butyrate enhances transcription by other mechanisms as well. Biotechnol. Bioeng. 2008;100: 189–194. © 2007 Wiley Periodicals, Inc.
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Use of histone deacetylase inhibitors such as NaB and VPA may also have undesired secondary effects, such as blocking cell cycle or inducing apoptosis.
“However, the use of these inhibitors may also have undesired secondary effects, such as blocking cell cycle or inducing apoptosis (Sung et al., 2004;Jiang and Sharfstein, 2008;Sunley and Butler, 2010).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Jiang and Sharfstein, 2008
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- Authors
- Jiang, Z., & Sharfstein, S. T.
- Affiliations
- Rensselaer Polytechnic Institute (US)
- Corresponding author
- Sharfstein, Susan T.
- Venue
- Biotechnology and Bioengineering
- Publisher
- Wiley
- Published
- 2007-11-19
- Volume
- 100
- Issue
- 1
- Pages
- 189-194
- ISSN
- 0006-3592 (ISSN-L)
- 1097-0290
- OpenAlex
- W2149145325
- Cited by
- 118
- References
- 23
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 11 · 2023: 4 · 2022: 3 · 2021: 13 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 1 · 2015: 8 · 2014: 8 · 2013: 10 · 2012: 7
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biotechnology and Bioengineering (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- sodium butyrate, CHO cells, gene accessibility, immunoglobulin heavy chain genes, light chain genes, recombinant protein productivity, DNase I footprinting, transcriptional regulation, apoptosis
- MeSH terms
- Animals, Antibodies, Monoclonal, Butyrates, Cell Survival, Cricetulus, Cricetinae, Recombinant Proteins, Protein Engineering, Up-Regulation, Gene Expression, CHO Cells, Genetic Enhancement, Cell Proliferation
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