• BMB Reports
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• v.54 no.2
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• pp.89-97
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• 2021

Post-transcriptional regulation is an indispensable cellular mechanism of gene expression control that dictates various cellular functions and cell fate decisions. Recently, various chemical RNA modifications, termed the "epitranscriptome," have been proposed to play crucial roles in the regulation of post-transcriptional gene expression. To date, more than 170 RNA modifications have been identified in almost all types of RNA. As with DNA modification-mediated control of gene expression, regulation of gene expression via RNA modification is also accomplished by three groups of proteins: writers, readers, and erasers. Several emerging studies have revealed that dysregulation in RNA modification is closely associated with tumorigenesis. Notably, the molecular outcomes of specific RNA modifications often have opposite cellular consequences. In this review, we highlight the current progress in the elucidation of the mechanisms of cancer development due to chemical modifications of various RNA species.

• Journal of Pharmaceutical Investigation
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• v.32 no.2
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• pp.65-72
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• 2002

Recently, stem cell-mediated gene therapy is emerging as a novel therapeutic approach. For the successful gene modification of stem cells, the development of a suitable gene transfer technique needs to be preceded. This review focuses on the various gene transfer techniques based on nonviral and viral vectors, and physical methods. The advantages and disadvantages of each gene transfer method are compared, and the general properties of these vectors are discussed in relation to the gene transfer in stem cell research. This review also highlights the therapeutic application of stem cell-mediated gene therapy. The choice of gene transfer vectors may vary depending on the type of the stem cells and the target of stem cell therapy. Of various gene transfer methods, viral vector-based gene therapy has been emphasized due to the higher transfection efficiency. The current status and up-to-date findings of stem cell-mediated gene therapy are discussed in the viewpoint of the various targets of stem cell therapy such as the modification of stem cell potency, the acceleration of regeneration process and the formation of expressional organization.

• Bulletin of the Korean Chemical Society
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• v.22 no.10
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• pp.1069-1075
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• 2001

• BMB Reports
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• v.51 no.5
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• pp.211-218
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• 2018

Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation. Although the underlying mechanisms suggesting how histone cleavage affects gene expression in view of chromatin structure are only beginning to be understood, it is clear that this process is a novel transcriptional epigenetic mechanism involving chromatin dynamics. In this review, we describe the functional properties of the known histone tail cleavage with its proteolytic enzymes, discuss how histone cleavage impacts gene expression, and present future directions for this area of study.

• Korean Journal of Microbiology
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• v.25 no.1
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• pp.40-45
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• 1987

The gene for the Bdi I modification enzyme, which is one of Bdi I restriction-modification system, fromBrevibacterium divaricatum FERM 5948 was cloned and expressed in E. coli. For cloning of the Bdi I methylase gene, we have initially used three cloning site(EcoRI, BamHI and Sal I) of plasmid vector pBR 322 and adopted the retransformation method after Bdi I restriction endonuclease cleavage. Selection of transformants carrying the gene was based on the resistance of the modified plasmid encoding the enzyme to cleavage by Bdi I restriction enzyme, and the recombinant plasmid pBDIM 116 containing 5.6kb EcoRI insery was proved to carry the gene. Crude cell extracts prepared from strains carrying the plasmid pBDIM 116 contained an S-adenosylmethionine-dependent methyltransferase activity specific for the Bdi I recognition site, ATCGAT. The restriction map was constructed with 11 restriction enzyme, and the Bdi I restriction-modification system was also discussed.

• Bulletin of the Korean Chemical Society
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• v.22 no.1
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• pp.46-52
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• 2001

To evaluate the non-ionic polymer, poly(ethylene glycol) (PEG), as a component in cationic copolymers for non-viral gene delivery systems, PEG was coupled to polyethylenimine (PEI). We present the effects of different degrees and shapes of pegylation of PEI on cytotoxicity, water solubility and transfection efficiency. This work reports the synthesis and characterization of a series of cationic copolymers on the basis of the conjugates of PEI with PEG. The modified molecules were significantly less toxic than the original polymer. Moreover, the chemical modification led to enhancement of their solubility. The comparison of pegylated PEIs with different degrees of derivation showed that all the polymers tested reached comparable levels of transgene expression to that of native PEI. As assessed by agarose gel electrophoresis, even highly substituted PEI derivatives were still able to form polyionic complexes with DNA. However, aside from an increase in solubility and retention of the ability to condense DNA, methoxy-PEG-modified PEIs resulted in a significant decrease in the transfection activity of the DNA complexes. In fact, the efficiency of the copolymer was compromised even at a low degree of modification suggesting that the PEG action resulting from its shape is important for efficient gene transfer. The mode of PEG grafting and the degree of modification influenced the transfection efficiency of PEI.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.35-39
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• 1997

Recent development of human genetics and techniques of gene transfer and expression have opened the way for investigating novel approaches based on the genetic modification of cells to treat both inherited and acquired diseases. This approach is referred to as gene therapy. Over the past few years, gene therapy has moved from the laboratory to phase I clinical trials. Although the clinical performance of gene transfer experiments is still in an early phase of development, the NIH of Health Recombinant DNA Advisory Comittee (RAC) has approved more than 150 protocols that involve gene transfer or putative gene therapy procedures in clinical settings. Many sectors of society in United States have participated in the design and formulation of these clinical trials through local Institutional Review Boards, the National Institutes of Health (NIH) RAC, the Chemotherapy Evaluation Program of the National Cancer institute, and the FDA. Currently, clinical trials involving gene modification are under way at many medical centers throughout the United Slates. The goals of these trials are as follows. (1) The design should be directed to short-term achievable goals. (2) Each clinical trial is best considered as an intermediate step in a multistep process. (3) The design should identify evaluable proximate endpoints for toxicity and for efficacy, (4) The potential benefits and possible risks for patients participating in these trial should be defined.

• Toxicological Research
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• v.31 no.1
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• pp.1-9
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• 2015

Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation, histone modification, and non-coding RNA expression. Heavy metals influence gene expression by epigenetic mechanisms and by directly binding to various metal response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. Here, we focus on recent advances in understanding epigenetic changes, gene expression, and biological effects induced by toxic metals.

• Animal Bioscience
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• v.36 no.2_spc
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• pp.333-338
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• 2023

Genetic modification enables modification of target genes or genome structure in livestock and experimental animals. These technologies have not only advanced bioscience but also improved agricultural productivity. To introduce a foreign transgene, the piggyBac transposon element/transposase system could be used for production of transgenic animals and specific target protein-expressing animal cells. In addition, the clustered regularly interspaced short palindromic repeat-CRISPR associated protein 9 (CRISPR-Cas9) system have been utilized to generate chickens with knockout of G0/G1 switch gene 2 (G0S2) and myostatin, which are related to lipid deposition and muscle growth, respectively. These experimental chickens could be the invaluable genetic resources to investigate the regulatory pathways and mechanisms of improvement of economic traits such as fat quantity and growth. The gene-edited animals could also be applicable to the livestock industry.

• BMB Reports
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• v.53 no.5
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• pp.266-271
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• 2020

Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great correlation with gene expression. A list of signature genes was defined as active (highly enriched H3K4me3), including NOVA1, NAT8L, and MMP16, and repressive genes (highly enriched H3K27me3), IRX2 and ADRB2, according to the distribution of these histone modifications on the promoter regions. To further enhance the investigation, potential candidates were also compared with other types of breast cancer to identify signs specific to TNBC. RNA-seq data was implemented to confirm and verify gene regulation governed by the histone modifications. Combinations of the biomarkers based on H3K4me3 and H3K27me3 showed the diagnostic value AUC 93.28% with P-value of 1.16e-226. The results of this study suggest that histone modification analysis of opposing histone modifications may be valuable toward developing biomarkers and targets for TNBC.