• Development and Reproduction
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• v.15 no.4
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• pp.273-279
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• 2011

Epigenetic regulation is a phenomenon that changes the gene function without changing the underlying DNA sequences. Epigenetic status of chromosome is regulated by mechanisms such as histone modification, DNA modification, and RNAi silencing. In this review, we focused on histone methylation for epigenetic regulation in ES cells. Two antagonizing multiprotein complexes regulate methylation of histones to guide expression of genes in ES cells. The Polycomb repressive complex 2 (PRC2), including EED, EZH2, and SUZ12 as core factors, contributes to gene repression by increasing trimethylation of H3K27 (H3K27me3). In contrast, the Trithorax group (TrxG) complex including MLL is related to gene activation by making H3K4me3. PRC2 and TrxG accompany a variety of accessory proteins. Most prominent feature of epigenetic regulation in ES cells is a bivalent state in which H3K27me3 and H3K4me3 appear simultaneously. Concerted regulation of PRC2, TrxG complex, and H3K4- or H3K27-specific demethylases activate expression of pluripotency-related genes and suppress development-related genes in ES cells. Modified balance of the regulators also enables ES cells to efficiently differentiate to a variety of cells upon differentiating signals. More detailed insights on the epigenetic regulators and their action will lead us to better understanding and use of ES cells for future application.

• Journal of Life Science
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• v.31 no.11
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• pp.995-1003
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• 2021

Chromatin remodeling regulates gene expression through epigenetic mechanisms. Aberrations in histone modification have been associated with depression-like behaviors in animal models. Additionally, growing evidence also indicates that epigenetic modification is associated with depression. p11 (S100A10) has been implicated in the pathophysiology of depression both in human and rodent models. In the present study, we investigated alterations in histone acetylation and methylation at the promoter of the p11 gene in the hippocampus of mice subjected to chronic unpredictable stress (CUS). C57BL/6 mice were exposed to CUS daily for 3 weeks. Depression-like behaviors were measured with the forced swimming test (FST). The levels of hippocampal p11 expression were analyzed by quantitative real-time polymerase chain reaction (PCR) and Western blotting. The levels of acetylated and methylated histone H3 at the promoter of p11 were measured by chromatin immunoprecipitation followed by real-time PCR. CUS-exposed mice displayed depression-like behaviors with prolonged immobility in FST. CUS led to significant decreases in the expression of p11 at both protein and mRNA levels. Meanwhile, there was a decrease in histone H3 acetylation (Ac-H3) and H3-K4 trimethylation (H3K4met3) and an increase in H3-K27 trimethylation (H3K27met3) at the p11 promoter. These results indicate that chronic stress causes the epigenetic suppression of p11 expression in the hippocampus.

• Journal of Life Science
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• v.25 no.6
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• pp.703-708
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• 2015

Hox genes encode a highly conserved family of homeodomain-containing transcription factors controlling vertebrate pattern formation along the anteroposterior body axis during embryogenesis. Retinoic acid (RA) is a key morphogen in embryogenesis and a critical regulator of both adult and embryonic cellular activity. Specifically, RA regulates Hox gene expression in mouse- or human-derived embryonic carcinoma (EC) cells. Histone modification has been reported to play a pivotal role in the process of RA-induced gene expression and cell differentiation. As histone modification is thought to play an essential role in RA-induced Hox gene expression, we examined RA-induced initiation of collinear expression of Hox genes and the corresponding histone modifications in F9 murine embryonic teratocarcinoma (EC) cells. Hox expression patterns and histone modifications were analyzed by semiquantitative RT-PCR, RNA-sequencing, and chromatin immuno-precipitation (ChIP)-PCR analyses. The Hoxc4 gene (D0) was initiated earlier than the Hoxc5 to –c10 genes (D3) upon RA treatment (day 0 [D0], day 1 [D1], and day 3 [D3]). The Hox nonexpressing D0 sample had a strong repressive marker, H3K27me3, than the D1 and D3 samples. In the D1 and D3 samples, reduced enrichment of the H3K27me3 marker was observed in the whole cluster. The active H3K4me3 marker was closely associated with the collinear expression of Hoxc genes. Thus, the Hoxc4 gene (D1) and all Hoxc genes (D3) expressed H3K4me3 upon transcription activation. In conclusion, these data indicated that removing H3K27me3 and acquiring H3K4me3 regulated RA-induced Hoxc gene collinearity in F9 cells.

• BMB Reports
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• v.40 no.2
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• pp.135-141
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• 2007

Conjugation of the methyl group at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3' sequence (DNA methylation) is the best studied epigenetic mechanism, which acts together with other epigenetic entities: histone modification, chromatin remodeling and microRNAs to shape the chromatin structure of DNA according to its functional state. The cancer genome is frequently characterized by hypermethylation of specific genes concurrently with an overall decrease in the level of 5-methyl cytosine, the pathological implication of which to the cancerous state has been well established. While the latest genome-wide technologies have been applied to classify and interpret the epigenetic layer of gene regulation in the physiological and disease states, the epigenetic testing has also been seriously explored in clinical practice for early detection, refining tumor staging and predicting disease recurrence. This critique reviews the latest research findings on the use of DNA methylation in cancer diagnosis, prognosis and staging/classification.

• BMB Reports
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• v.45 no.11
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• pp.604-611
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• 2012

Recent advances in genome and transcriptome analysis have enabled identification of numerous members of a new class of noncoding RNA, long noncoding RNA (lncRNA). lncRNAs are broadly defined as RNA molecules greater than 200 nt in length and lacking an open reading frame. Recent studies provide evidence that lncRNAs play central roles in a wide range of cellular processes through interaction with key component proteins in the gene regulatory system, and that alteration of their cell- or tissue-specific expression and/or their primary or secondary structures is thought to promote cell proliferation, invasion and metastasis. The biological and molecular characteristics of the large majority of lncRNAs remains unknown, and it is anticipated that improved understanding of the roles played by lncRNAs in cancer will lead to the development of novel biomarkers and effective therapeutic strategies.

• Animal cells and systems
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• v.11 no.2
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• pp.93-98
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• 2007

Gonadotropin-releasing hormone (GnRH), synthesized in the hypothalamus, plays a pivotal role in the regulation of vertebrate reproduction. Since molecular isoforms of GnRH and their receptors (GnRHR) have been isolated in a broad range of vertebrate species, GnRH and GnRHR provide an excellent model for understanding the molecular co-evolution of a peptide ligand-receptor pair. Vertebrate species possess multiple forms of GnRH, which have been created through evolutionary mechanisms such as gene/chromosome duplication, gene deletion and modification. Similar to GnRHs, GnRH receptors (GnRHR) have also been diversified evolutionarily. Comparative ligand-receptor interaction studies for non-mammalian and mammalian GnRHRs combined with mutational mapping studies of GnRHRs have aided the identification of domains or motifs responsible for ligand binding and receptor activation. Here we discuss the molecular basis of GnRH-GnRHR co-evolution, particularly the structure-function relationship regarding ligand selectivity and signal transduction of mammalian and non-mammalian GnRHRs.

• BMB Reports
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• v.43 no.12
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• pp.781-788
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• 2010

An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.26-26
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• 2001

8-Hydroxyguanine(oh$\^$8/Gua), an oxidative DNA adduct is a most easily and abundantly formed base modification. What we have known about oh$\^$8/Gua so far is that this DNA adduct mediates the mutagenesis and it is used as a useful marker of oxidative DNA damage. We found additional evidence and here present them: 1) oh$\^$8/Gua in DNA can trigger cell death by inducing cell cycle arrest and apoptosis and 2) it can be used to assess the oxidative damage of each individual gene.(omitted)

• BMB Reports
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• v.28 no.6
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• pp.494-498
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• 1995

Maize mitochondrial tRNAs for isoleucine have been isolated using a putative $tRNA^{Ile}$ gene probe which has been previously isolated and characterized. It contains the 5'-CAT anticodon which would normally recognize the AUG methionine codon. The nucleotide sequence of one of these tRNAs has been partially determined, and contains a modified nucleotide at the first position of the anticodon. This type of posttranscriptional modification event could change the specificity of amino acid acceptance of a tRNA, unlike that deduced from the corresponding gene. An aminoacylation experiment also demonstrated that these purified tRNAs have isoleucine acceptance activity but no methionine-accepting activity.

• Proceedings of the KSAR Conference
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• 2001.10a
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• pp.48-49
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• 2001

While transgenic manipulation in mice have been very successful the same is not true for cattle and pigs. The inability to isolate ES cells from the bovine and porcine has precluded the utilization of the gene targeting technology in these species. Fortunately new advances in cloning by nuclear transfer have opened up a unique opportunity to undertake precise genetic modification in cattle and pigs. The ability of a number of different laboratory groups to successfully clone cattle is due to numerous research programs focused on nuclear transfer in cattle, and the enormous base of knowledge developed over the last 20 years involving the application of assisted reproductive techniques in cattle. Successful and repeatable procedures for in vitro oocyte maturation, in vitro fertilization, and in vitro embryo culture are now well established for cattle. In our laboratory we have utilized nuclear transfer to reproduce the genotypes of several animals, selected for cloning based on their inherent genetic value. Results that we have obtained to date are similar to those reported by other laboratories. (omitted)