Sodium butyrate stimulates monoclonal antibody over-expression in CHO cells by improving gene accessibility

Jiang, Z; Sharfstein, ST

HERO ID

1458177

Reference Type

Journal Article

Year

2008

Language

English

PMID

18023047

HERO ID 1458177
In Press No
Year 2008
Title Sodium butyrate stimulates monoclonal antibody over-expression in CHO cells by improving gene accessibility
Authors Jiang, Z; Sharfstein, ST
Journal Biotechnology and Bioengineering
Volume 100
Issue 1
Page Numbers 189-194
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.
Doi 10.1002/bit.21726
Pmid 18023047
Wosid WOS:000254786200020
Is Certified Translation No
Dupe Override No
Comments Source: Web of Science WOS:000254786200020
Is Public Yes
Language Text English
Keyword sodium butyrate; transcriptional regulation; DNase footprinting; CHO cells; recombinant monoclonal antibodies