ArticleNucleic acids research2010
The impact of intragenic CpG content on gene expression.
Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Gene therapy for hemophilia B: results from the phase 1/2 101HEMB01/02 studies.Blood advances · 2025Trial
- Impact of GC content on de novo gene birth.Nature communications · 2026Article
- Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF.Protein science : a publication of the Protein Society · 2025Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- An investigation of codon usage pattern analysis in pancreatitis associated genes.BMC genomic data · 2022Article
- RBM33 directs the nuclear export of transcripts containing GC-rich elements.Genes & development · 2022Article
- Strong Selectional Forces Fine-Tune CpG Content in Genes Involved in Neurological Disorders as Revealed by Codon Usage Patterns.Frontiers in neuroscience · 2022Article
- Minimal impact of ZAP on lentiviral vector production and transduction efficiency.Molecular therapy. Methods & clinical development · 2021Article
- Genes Common in Primary Immunodeficiencies and Cancer Display Overrepresentation of Codon CTG and Dominant Role of Selection Pressure in Shaping Codon Usage.Biomedicines · 2021Article
- Increased CFTR expression and function from an optimized lentiviral vector for cystic fibrosis gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines.Pharmaceutics · 2021Review
- Codon Usage and Splicing Jointly Influence mRNA Localization.Cell systems · 2020Article
- Limited expression of non-integrating CpG-free plasmid is associated with increased nucleosome enrichment.PloS one · 2020Article
- Effects of codon optimization on coagulation factor IX translation and structure: Implications for protein and gene therapies.Scientific reports · 2019Article
- Optimizing a Human Papillomavirus Type 16 L1-Based Chimaeric Gene for Expression in Plants.Frontiers in bioengineering and biotechnology · 2018Article
- Codon-Optimized P1A-Encoding DNA Vaccine: Toward a Therapeutic Vaccination against P815 Mastocytoma.Molecular therapy. Nucleic acids · 2017Article
- MeDIP-seq and nCpG analyses illuminate sexually dimorphic methylation of gonadal development genes with high historic methylation in turtle hatchlings with temperature-dependent sex determination.Epigenetics & chromatin · 2017Article
- Rational Development of A Polycistronic Plasmid with A CpG-Free Bacterial Backbone as A Potential Tool for Direct Reprogramming.Cell journal · 2017Article
- Damage-inducible intragenic demethylation of the human TP53 tumor suppressor gene is associated with transcription from an alternative intronic promoter.Molecular carcinogenesis · 2016Article
- Evaluating the use of a CpG free promoter for long-term recombinant protein expression stability in Chinese hamster ovary cells.BMC biotechnology · 2016Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of vaccine components or recombinant therapeutics critically depends on sustained expression of the corresponding transgene. This study aimed to determine the contribution of intragenic CpG content to expression efficiency in transiently and stably transfected mammalian cells. Based upon a humanized version of green fluorescent protein (GFP) containing 60 CpGs within its coding sequence, a CpG-depleted variant of the GFP reporter was established by carefully modulating the codon usage. Interestingly, GFP reporter activity and detectable protein amounts in stably transfected CHO and 293 cells were significantly decreased upon CpG depletion and independent from promoter usage (CMV, EF1 alpha). The reduction in protein expression associated with CpG depletion was likewise observed for other unrelated reporter genes and was clearly reflected by a decline in mRNA copy numbers rather than translational efficiency. Moreover, decreased mRNA levels were neither due to nuclear export restrictions nor alternative splicing or mRNA instability. Rather, the intragenic CpG content influenced de novo transcriptional activity thus implying a common transcription-based mechanism of gene regulation via CpGs. Increased high CpG transcription correlated with changed nucleosomal positions in vitro albeit histone density at the two genes did not change in vivo as monitored by ChIP.
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Registered trials
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