Organization of Plasmid DNA into Nucleosome-Like Structures after Transfection in Eukaryotic Cells

Mladenova, Veronika; Mladenov, Emil; Russev, George

doi:10.1080/13102818.2009.10817609

Cited by 28 publications

(16 citation statements)

References 19 publications

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“…In further support of the notion that plasmid DNA transactions can be reflective of genomic DNA transactions, it appears that plasmids are readily complexed into a nucleosomal structure in human cells, i.e. they become chromatinized (133-136). Moreover, plasmid DNA damage induces histone modifications that affect expression of plasmid DNA (137), indicating a functional plasmid-chromatin structure.…”

Section: Evidence Of Inter-individual Drc Differences From Direct mentioning

confidence: 88%

Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research

2014

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Why does a constant barrage of DNA damage lead to disease in some individuals, while others remain healthy? This article surveys current work addressing the implications of inter-individual variation in DNA repair capacity for human health, and discusses the status of DNA repair assays as potential clinical tools for personalized prevention or treatment of disease. In particular, we highlight research showing that there are significant inter-individual variations in DNA Repair Capacity (DRC), and that measuring these differences provides important biological insight regarding disease susceptibility and cancer treatment efficacy. We emphasize work showing that it is important to measure repair capacity in multiple pathways, and that functional assays are required to fill a gap left by genome wide association studies, global gene expression and proteomics. Finally, we discuss research that will be needed to overcome barriers that currently limit the use of DNA repair assays in the clinic.

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Section: Evidence Of Inter-individual Drc Differences From Direct mentioning

confidence: 88%

Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research

2014

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“…These assays are not influenced by endogenous chromatin compaction or epigenetic modifications and test the potential enhancer capability of each specific cis-regulatory element 17 .…”

Section: Introductionmentioning

confidence: 99%

Functional mapping of androgen receptor enhancer activity

Huang

Lingadahalli

Morova

et al. 2020

Preprint

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Androgen receptor (AR) is critical to the initiation, growth and progression of almost all prostate cancers. Once activated, the AR binds to cis-regulatory enhancer elements on DNA that drive gene expression. Yet, there are 10-100x more binding sites than differentially expressed genes. It still remains unclear how individual sites contribute to AR-mediated transcription. While descriptive functional genomic approaches broadly correlate with enhancer activity, they do not provide the locus-specific resolution needed to delineate the underlying regulatory logic of AR- mediated transcription. Therefore, we functionally tested all commonly occuring clinical AR binding sites with Self-Transcribing Active Regulatory Regions sequencing (STARRseq) to generate the first map of intrinsic AR enhancer activity. This approach is not significantly affected by endogenous chromatin modifications and measures the potential enhancer activity at each cis- regulatory element. Interestingly we found that only 7% of AR binding sites displayed increased enhancer activity upon hormonal stimulation. Instead, the vast majority of AR binding sites were either inactive (81%) or constitutively active enhancers (11%). These annotations strongly correlated with enhancer-associated features in both cell line and clinical prostate cancer. With these validated annotations we next investigated the effect of each enhancer class on transcription and found that AR-driven inducible enhancers frequently interacted with promoters, forming central chromosomal loops critical for gene transcription. We demonstrated that these inducible enhancers act as regulatory hubs that increase contacts with both other AR binding sites and gene promoters. This functional map was used to identify a somatic mutation that significantly reduces the expression of a commonly mutated AR-regulated tumour suppressor. Together, our data reveal a complex interplay between different AR binding sites that work in a highly coordinated manner to drive gene transcription.

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“…As previously reported, histone acetylation mainly occurs on lysine residues, making chromatin structure loose and promoting gene expression; however, deacetylation of histones represses gene expression [18]. Another study revealed that nucleosome-like particles could be formed on plasmid DNA after transient transfection [19]. Thus, we hypothesized that after transient transfection, the plasmids would enter the nucleus and form complexes with histones.…”

Section: Discussionmentioning

confidence: 71%

High-Throughput Screening Identifies Two Novel Small Molecule Enhancers of Recombinant Protein Expression

et al. 2020

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As a primary strategy for production of biological drugs, recombinant proteins produced by transient transfection of mammalian cells are essential for both basic research and industrial production. Here, we established a high-throughput screening platform for improving the expression levels of recombinant proteins. In total, 10,011 small molecule compounds were screened through our platform. After two rounds of screening, we identified two compounds, Apicidin and M-344, that significantly enhanced recombinant protein expression. Both of the selected compounds were histone deacetylase inhibitors, suggesting that the two small molecules increased the expression levels of recombinant proteins by promoting histone acetylation. Moreover, both molecules showed low cytotoxicity. Therefore, our findings suggest that these small molecules may have wide applications in the future.

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Organization of Plasmid DNA into Nucleosome-Like Structures after Transfection in Eukaryotic Cells

Cited by 28 publications

References 19 publications

Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research

Inter-individual variation in DNA repair capacity: A need for multi-pathway functional assays to promote translational DNA repair research

Functional mapping of androgen receptor enhancer activity

High-Throughput Screening Identifies Two Novel Small Molecule Enhancers of Recombinant Protein Expression

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