scholarly journals Gene Amplification and the Extrachromosomal Circular DNA

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1533
Author(s):  
Noriaki Shimizu
Keyword(s):  
Gene Amplification ◽  
Malignant Tumors ◽  
Human Cancer ◽  
Replication Initiation ◽  
Matrix Attachment Region ◽  
Genome Plasticity ◽  
Sequence Element ◽  
Circular Dna ◽  
Attachment Region ◽  
Human Malignant Tumors

Oncogene amplification is closely linked to the pathogenesis of a broad spectrum of human malignant tumors. The amplified genes localize either to the extrachromosomal circular DNA, which has been referred to as cytogenetically visible double minutes (DMs), or submicroscopic episome, or to the chromosomal homogeneously staining region (HSR). The extrachromosomal circle from a chromosome arm can initiate gene amplification, resulting in the formation of DMs or HSR, if it had a sequence element required for replication initiation (the replication initiation region/matrix attachment region; the IR/MAR), under a genetic background that permits gene amplification. In this article, the nature, intracellular behavior, generation, and contribution to cancer genome plasticity of such extrachromosomal circles are summarized and discussed by reviewing recent articles on these topics. Such studies are critical in the understanding and treating human cancer, and also for the production of recombinant proteins such as biopharmaceuticals by increasing the recombinant genes in the cells.

scholarly journals Episomal vectors based on S/MAR and the β-globin Replicator, encoding a synthetic transcriptional activator, mediate efficient γ-globin activation in haematopoietic cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Eleana F. Stavrou ◽  
Emannuouil Simantirakis ◽  
Meletios Verras ◽  
Carlos Barbas ◽  
George Vassilopoulos ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Bone Marrow Cells ◽  
Globin Gene ◽  
K562 Cells ◽  
Replication Initiation ◽  
Matrix Attachment Region ◽  
Globin Mrna ◽  
Dna Replication Initiation ◽  
Episomal Vectors ◽  
Attachment Region

AbstractWe report the development of episomal vectors for the specific γ-globin transcription activation in its native position by activator Zif-VP64, based on the Scaffold/Matrix Attachment Region (S/MAR) for episomal retention and the β-globin Replicator, the DNA replication-Initiation Region from the β-globin locus. Vector Zif-VP64-Ep1 containing transcription cassettes CMV- Zif-VP64 and CMV-eGFP-S/MAR transfected a)K562 cells; b)murine β-YAC bone marrow cells (BMC); c)human haematopoietic progenitor CD34+ cells, with transfection efficiencies of 46.3 ± 5.2%, 23.0 ± 2.1% and 24.2 ± 2.4% respectively. K562 transfections generated stable cell lines running for 28 weeks with and without selection, with increased levels of γ-globin mRNA by 3.3 ± 0.13, of γ-globin protein by 6.75 ± 3.25 and HbF protein by 2 ± 0.2 fold, while the vector remained episomal and non integrated. In murine β-YAC BMCs the vector mediated the activation of the silent human γ-globin gene and in CD34+ cells, increased γ-globin mRNA, albeit only transiently. A second vector Zif-VP64-Ep2, with both transcription cassettes carrying promoter SFFV instead of CMV and the addition of β-globin Replicator, transferred into CD34+ cells, produced CD34+ eGFP+ cells, that generated colonies in colony forming cell cultures. Importantly, these were 100% fluorescent, with 2.11 ± 0.13 fold increased γ-globin mRNA, compared to non-transfected cells. We consider these episomal vectors valid, safer alternatives to viral vectors.

scholarly journals The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases

2021 ◽  
Vol 22 (5) ◽  
pp. 2318
Author(s):  
Lyes Toualbi ◽  
Maria Toms ◽  
Mariya Moosajee
Keyword(s):  
Viral Vectors ◽  
Matrix Attachment Region ◽  
Great Promise ◽  
Viral Gene ◽  
Retinal Diseases ◽  
Gene Copies ◽  
Augmentation Strategies ◽  
Viral Gene Therapy ◽  
Effective Option ◽  
Attachment Region

Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Here, we review the advances in non-viral gene augmentation strategies, such as the use of plasmids with minimal bacterial backbones and scaffold/matrix attachment region (S/MAR) sequences, that have the capability to overcome these weaknesses by accommodating genes of any size and maintaining episomal transgene expression with a lower risk of eliciting an immune response. Low retinal transfection rates remain a limitation, but various strategies, including coupling the DNA with different types of chemical vehicles (nanoparticles) and the use of electrical methods such as iontophoresis and electrotransfection to aid cell entry, have shown promise in preclinical studies. Non-viral gene therapy may offer a safer and effective option for future treatment of IRDs.

scholarly journals Screening of a Protein That Interacts with the Matrix Attachment Region-Binding Protein fromDunaliella salina

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Rui Yang ◽  
Zhaoxi Li ◽  
Yan Lin ◽  
Baosheng Yang ◽  
Tianyun Wang
Keyword(s):  
Binding Protein ◽  
Matrix Attachment Region ◽  
Regulatory Function ◽  
Glutathione S Transferase ◽  
Reading Frame ◽  
Cis Acting ◽  
Binding Partner ◽  
The Matrix ◽  
Attachment Region ◽  
Regulated Functions

We isolated the matrix attachment region-binding protein (MBP) DMBP-1 fromDunaliella salinain our previous studies. MBPs are part of the cis-acting protein family cluster. The regulatory function possibly works through the interaction of the MBPs with each other. In the present study, DMBP-1 was used as the bait in screening theD. salinacDNA library for DMBP-1 interactors that could potentially mediate the DMBP-1-regulated functions. A novel MBP, namely, DMBP-2, was identified as a DMBP-1 binding partner. The cDNA of DMBP-1 was 823 bp long and contained a 573 bp open reading frame, which encoded a polypeptide of 191 amino acids. The interaction between DMBP-2 and DMBP-1 was further confirmed through glutathione S-transferase pull-down assays.

scholarly journals Critical roles of the immunoglobulin intronic enhancers in maintaining the sequential rearrangement of IgH and Igk loci

2006 ◽  
Vol 203 (7) ◽  
pp. 1721-1732 ◽  
Author(s):  
Matthew A. Inlay ◽  
Tongxiang Lin ◽  
Heather H. Gao ◽  
Yang Xu
Keyword(s):  
B Cells ◽  
Developmental Stage ◽  
Heavy Chain ◽  
Light Chain ◽  
Matrix Attachment Region ◽  
Cis Elements ◽  
Wild Type ◽  
Intronic Enhancer ◽  
Attachment Region

V(D)J recombination of immunoglobulin (Ig) heavy (IgH) and light chain genes occurs sequentially in the pro– and pre–B cells. To identify cis-elements that dictate this order of rearrangement, we replaced the endogenous matrix attachment region/Igk intronic enhancer (MiEκ) with its heavy chain counterpart (Eμ) in mice. This replacement, denoted EμR, substantially increases the accessibility of both Vκ and Jκ loci to V(D)J recombinase in pro–B cells and induces Igk rearrangement in these cells. However, EμR does not support Igk rearrangement in pre–B cells. Similar to that in MiEκ−/− pre–B cells, the accessibility of Vκ segments to V(D)J recombinase is considerably reduced in EμR pre–B cells when compared with wild-type pre–B cells. Therefore, Eμ and MiEκ play developmental stage-specific roles in maintaining the sequential rearrangement of IgH and Igk loci by promoting the accessibility of V, D, and J loci to the V(D)J recombinase.

scholarly journals Variant Chromatin Structure of theoriP Region of Epstein-Barr Virus and Regulation of EBER1 Expression by Upstream Sequences andoriP

2001 ◽  
Vol 75 (13) ◽  
pp. 6235-6241 ◽  
Author(s):  
Barbara Wensing ◽  
Albert Stühler ◽  
Peter Jenkins ◽  
Martine Hollyoake ◽  
Claudio Elgueta Karstegl ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Virus Genome ◽  
Micrococcal Nuclease ◽  
Matrix Attachment Region ◽  
Barr Virus ◽  
Latently Infected ◽  
Attachment Region ◽  
Nuclear Matrix Attachment Region ◽  
Epstein Barr ◽  
Nucleosomal Structure

ABSTRACT Most of the Epstein-Barr virus genome in latently infected cells is in a standard nucleosomal structure, but the region encompassingoriP and the Epstein-Barr virus-encoded small RNA (EBER) genes shows a distinctive pattern when digested with micrococcal nuclease. This pattern corresponds to a previously mapped nuclear matrix attachment region. Although the EBER genes are adjacent to oriP, there is only a two- to fourfold effect oforiP on EBER expression. However, sequences containing a consensus ATF site upstream of EBER1 are important for EBER1 expression.

Variations in lymphokine generation by individual lymph nodes draining human malignant tumors

1989 ◽  
Vol 30 (5) ◽  
pp. 277-282 ◽  
Author(s):  
Duan-Ren Wen ◽  
Dave SB Hoon ◽  
Cindy Chang ◽  
Alistair J. Cochran
Keyword(s):  
Lymph Nodes ◽  
Malignant Tumors ◽  
Human Malignant Tumors

The therapeutic value and molecular mechanisms of lncRNA FENDRR in human cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Wen Xu ◽  
Bei Wang ◽  
Yuxuan Cai ◽  
Jinlan Chen ◽  
Enqing Meng ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Human Cancer ◽  
Tumor Therapy ◽  
Pathophysiological Mechanism ◽  
Regulatory Processes ◽  
Carcinoma Prostate ◽  
Therapeutic Value ◽  
And Migration

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy. Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed. Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed. Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.

Sign in / Sign up

Export Citation Format

Share Document