• Restorative Dentistry and Endodontics
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• v.40 no.1
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• pp.14-22
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• 2015

Genetic information such as DNA sequences has been limited to fully explain mechanisms of gene regulation and disease process. Epigenetic mechanisms, which include DNA methylation, histone modification and non-coding RNAs, can regulate gene expression and affect progression of disease. Although studies focused on epigenetics are being actively investigated in the field of medicine and biology, epigenetics in dental research is at the early stages. However, studies on epigenetics in dentistry deserve attention because epigenetic mechanisms play important roles in gene expression during tooth development and may affect oral diseases. In addition, understanding of epigenetic alteration is important for developing new therapeutic methods. This review article aims to outline the general features of epigenetic mechanisms and describe its future implications in the field of dentistry.

• BMB Reports
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• v.44 no.3
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• pp.176-181
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• 2011

Inhibiting histone deacetylase (HDAC) activity modulates the epigenetic status of cells, resulting in an alteration of gene expression and cellular function. Here, we investigated the effects of HDAC inhibitors on mouse embryonic stem (ES) cells. The HDAC inhibitors trichostatin A, suberoylanilide hydroxamic acid, sodium butyrate, and valproic acid induced early differentiation of mouse ES cells and triggered induction of heat-shock protein (HSP)70. In contrast, class III HDAC inhibitors failed to induce differentiation or HSP70 expression. Transcriptional upregulation of HSP70 was confirmed by mRNA expression analysis, an inhibitor study, and chromatin immunoprecipitation. HSP70 induction was dependent on the SAPK/JNK, p38, and PI3K/Akt pathways. Differentiation and induction of HSP70 by a subset of HDAC inhibitors was also examined in human ES cells, which suggests that the phenomenon generally occurs in ES cells. A better understanding of the effects of HDAC inhibitors may give more insight into their application in stem cell biology.

• Korean Journal of Plant Resources
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• v.20 no.6
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• pp.518-523
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• 2007

Lunasin is small subunit peptide of coded from Gm2S-1 gene in soybean. It has been previously demonstrated that lunasin is a novel and promising cancer preventive peptide. Lunasin peptide is found only in the seed and not other tissues. And lunasin peptide starts to appear at 5 weeks after flowering and remains in the mature seed. We report here firstly lunasin peptide identified from soybean callus induced by the tissue culture and demonstrate its anticancer properties. The lunasin was identified and purified from soybean callus aged for 6 months. The callus lunasin($1{\mu}M$) inhibited the acetylation of histone H3 and H4 by 58.8% and 56.5%, respectively. And it fully inhibited foci formation compared to the values of the positive control(no lunasin) and negative control(no MCA). Purified lunasin was able to internalize into the cell and localized in the nucleus.

• Molecules and Cells
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• v.40 no.7
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• pp.485-494
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• 2017

Oleanolic acid (OA) has neurotrophic effects on neurons, although its use as a neurological drug requires further research. In the present study, we investigated the effects of OA and OA derivatives on the neuronal differentiation of rat hippocampal neural progenitor cells. In addition, we investigated whether the class II histone deacetylase (HDAC) 5 mediates the gene expression induced by OA. We found that OA and OA derivatives induced the formation of neurite spines and the expression of synapse-related molecules. OA and OA derivatives stimulated HDAC5 phosphorylation, and concurrently the nuclear export of HDCA5 and the expression of HDAC5 target genes, indicating that OA and OA derivatives induce neural differentiation and synapse formation via a pathway that involves HDAC5 phosphorylation.

• Molecules and Cells
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• v.27 no.4
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• pp.481-490
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• 2009

Diverse posttranslational modifications of histones, such as acetylation and methylation, play important roles in controlling gene expression. Histone methylation in particular is involved in a broad range of biological processes, including heterochromatin formation, X-chromosome inactivation, genomic imprinting, and transcriptional regulation. Recently, it has been demonstrated that proteins containing the Jumonji (Jmj) C domain can demethylate histones. In Arabidopsis, twenty-one genes encode JmjC domain-containing proteins, which can be clustered into five clades. To address the biological roles of the Arabidopsis genes encoding JmjC-domain proteins, we analyzed the temporal and spatial expression patterns of nine genes. RT-PCR analyses indicate all nine Arabidopsis thaliana Jmj (AtJmj) genes studied are actively expressed in various tissues. Furthermore, studies of transgenic plants harboring AtJmj::${\beta}$-glucuronidase fusion constructs reveal that these nine AtJmj genes are expressed in a developmentally and spatially regulated manner.

• Molecules and Cells
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• v.37 no.1
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• pp.43-50
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• 2014

Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

• Molecules and Cells
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• v.42 no.1
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• pp.17-27
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• 2019

Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.

• Journal of Microbiology and Biotechnology
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• v.25 no.5
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• pp.579-588
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• 2015

Fungi of the genus Pestalotiopsis have drawn attention for their capability to produce an array of bioactive secondary metabolites that have potential for drug development. Here, we report the determination of a polyketide derivative compound, pestalotiollide B, in the culture of the saprophytic fungus Pestalotiopsis microspora NK17. Structural information acquired by analyses with a set of spectroscopic and chromatographic techniques suggests that pestalotiollide B has the same skeleton as the penicillide derivatives, dibenzodioxocinones, which are inhibitors of cholesterol ester transfer protein (CETP), and as purpactins A and C', inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Strain NK17 can make a fairly high yield of pestalotiollide B (i.e., up to 7.22 mg/l) in a constitutive manner in liquid culture. Moreover, we found that a putative histone deacetylase gene, designated as hid1, played a role in the biosynthesis of pestalotiollide B. In the hid1 null mutant, the yield of pestalotiollide B increased approximately 2-fold to 15.90 mg/l. In contrast, deletion of gene hid1 led to a dramatic decrease of conidia production of the fungus. These results suggest that hid1 is a modulator, concerting secondary metabolism and development such as conidiation in P. microspora. Our work may help with the investigation into the biosynthesis of pestalotiollide B and the development for new CETP and ACAT inhibitors.

• Biomedical Science Letters
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• v.18 no.2
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• pp.165-168
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• 2012

Hox proteins containing DNA-binding homedomain act as transcription factors important for anteroposterior body patterning during vertebrate embryogenesis. However, the precise mechanisms by which signal pathways are transduced to regulate the Hox gene expression are not clear. In the course of an attempt to isolate an upstream regulatory factor(s) controlling Hox genes, protein kinase B alpha (Akt1) has been identified as a putative regulator of Hox genes through in silico analysis (GEO profile). In the Gene Expression Omnibus (GEO) dataset GDS1784 at the NCBI (National Center for Biotechnology Information) site, Hox genes were differentially expressed depending on the presence or absence of Akt1. Since it was not well known how Akt1 regulates the specific Hox genes, whose transcription was reported to be regulated by epigenetic modifications such as histone acetylation, methylation etc., the expression of Gcn5, a histone acetyltransferase (HAT), was analyzed in wild type (WT) as well as in $Akt1^{-/-}$ mouse embryonic fibroblast (MEF) cells. RT-PCR analysis revealed that the amount of Gcn5 mRNA was similar in both WT and $Akt1^{-/-}$ MEFs. However, the protein level of Gcn5 was significantly increased in $Akt1^{-/-}$ MEF cells. The half life of Gcn5 was 1 hour in wild type whereas 8 hours in $Akt1^{-/-}$ MEF. These data all together, indicate that Gcn5 is post-transcriptionally down-regulated and the protein stability is negatively regulated by Akt1 in MEF cells.

• Journal of Plant Biotechnology
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• v.35 no.2
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• pp.133-140
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• 2008

The modification of DNA and histone plays an important role for gene expression in plant development. The objective of this research is to observe the effects of methylation on the gene expression during dedifferentiation from rice mature seeds to callus and differentiation from callus to shoots. The embryogenic callus with ability to shoot regeneration was not induced on the N6A medium supplemented with 5-azacytidine and abnormal callus with brown color was formed. When the normal rice callus was placed on the regeneration MSRA medium supplemented with 5-azacytidine, the shoot regeneration was inhibited. The results showed that 5-azacytidine, DNA demethylating agent, had negative effects on normal embryogenic callus formation and shoot regeneration. This suggested that DNA methylation of some genes was required for normal cell dedifferentiation and differentiation in tissue culture. The microarray and $GeneFishig^{TM}$ DEG screening were used to observe the gene transcript profile in callus induction and regeneration on N6A (N6 medium + 5-azaC) and MSRA (MS regeneration medium + 5-azaC). Subsets of genes were up-regulated or down-regulated in response to 5-azaC treatments. The genes related with epigenetic regulation, electron transport, nucleic acid metabolism and response to stress were up and down regulated. The different expression of some genes (germin like protein etc.) during callus induction and shoot regeneration was confirmed using RT-PCR and northern blot analysis.