Addition of a histone deacetylase inhibitor increases recombinant protein expression in Medicago truncatula cell cultures

Rita B. Santos, Ana Sofia Pires, Rita Abranches

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Plant cell cultures are an attractive platform for the production of recombinant proteins. A major drawback, hindering the establishment of plant cell suspensions as an industrial platform, is the low product yield obtained thus far. Histone acetylation is associated with increased transcription levels, therefore it is expected that the use of histone deacetylase inhibitors would result in an increase in mRNA and protein levels. Here, this hypothesis was tested by adding a histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), to a cell line of the model legume Medicago truncatula expressing a recombinant human protein. Histone deacetylase inhibition by SAHA and histone acetylation levels were studied, and the effect of SAHA on gene expression and recombinant protein levels was assessed by digital PCR. SAHA addition effectively inhibited histone deacetylase activity resulting in increased histone acetylation. Higher levels of transgene expression and accumulation of the associated protein were observed. This is the first report describing histone deacetylase inhibitors as inducers of recombinant protein expression in plant cell suspensions as well as the use of digital PCR in these biological systems. This study paves the way for employing epigenetic strategies to improve the final yields of recombinant proteins produced by plant cell cultures.

Original languageEnglish
Article number16756
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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Medicago truncatula
Histone Deacetylase Inhibitors
Recombinant Proteins
Plant Cells
Cell Culture Techniques
Acetylation
Histones
Histone Deacetylases
Suspensions
Polymerase Chain Reaction
Proteins
Transgenes
Epigenomics
Fabaceae
Gene Expression
Cell Line
Messenger RNA
vorinostat

Cite this

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abstract = "Plant cell cultures are an attractive platform for the production of recombinant proteins. A major drawback, hindering the establishment of plant cell suspensions as an industrial platform, is the low product yield obtained thus far. Histone acetylation is associated with increased transcription levels, therefore it is expected that the use of histone deacetylase inhibitors would result in an increase in mRNA and protein levels. Here, this hypothesis was tested by adding a histone deacetylase inhibitor, suberanilohydroxamic acid (SAHA), to a cell line of the model legume Medicago truncatula expressing a recombinant human protein. Histone deacetylase inhibition by SAHA and histone acetylation levels were studied, and the effect of SAHA on gene expression and recombinant protein levels was assessed by digital PCR. SAHA addition effectively inhibited histone deacetylase activity resulting in increased histone acetylation. Higher levels of transgene expression and accumulation of the associated protein were observed. This is the first report describing histone deacetylase inhibitors as inducers of recombinant protein expression in plant cell suspensions as well as the use of digital PCR in these biological systems. This study paves the way for employing epigenetic strategies to improve the final yields of recombinant proteins produced by plant cell cultures.",
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Addition of a histone deacetylase inhibitor increases recombinant protein expression in Medicago truncatula cell cultures. / Santos, Rita B.; Pires, Ana Sofia; Abranches, Rita.

In: Scientific Reports, Vol. 7, No. 1, 16756, 01.12.2017.

Research output: Contribution to journalArticle

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