• BMB Reports
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• v.50 no.4
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• pp.162-163
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• 2017

RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects have been seen on genome-wide transcription under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes. Interestingly, a majority of Set2-repressed genes are overlapped by a lncRNA transcription that targets H3K36 methylation and deacetylation by Rpd3S HDAC to mRNA promoters. Furthermore, this pathway delays the induction of many cryptic transcripts upon environmental changes. Therefore, the Set2-Rpd3S HDAC pathway functions to fine-tune expression dynamics of mRNAs and ncRNAs.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2915-2918
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• 2013

Background: Recent studies have shown that 3-deazaneplanocin A (DZNep), a well-known histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and induces apoptosis, while inhibiting proliferation and metastasis, in cancer cells, including acute myeloid leukemia, breast cancer and glioblastoma. However, little is known about effects of DZNep on ovarian cancer cells. Materials and Methods: We here therefore studied DZNep-treated A2780 ovarian cancer cells in vitro. Proliferation of ovarian cancer cells under treatment of DZNep was assessed by MTT and apoptosis by flow cytometry. Cell wound healing was applied to detect the migration. Finally, we used q-PCR to assess the migration-related gene, E-cadherin. Results: DZNep could inhibit the proliferation of A2780 and induce apoptosis Furthermore, it inhibited migration and increased the expression of E-cadherin (P<0.05). Conclusion: DZNep is a promising therapeutic agent for ovarian cancer cells, with potential to inhibite proliferation, induce apoptosis and decrease migration.

• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.489-497
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• 1997

The distributions characteristics of neurons displaying immunoreactivity to the catecholamine synthetic enzymes, tyrosine hydroxylase(TH), dopamine-${\beta}$-hydroxylase(DBH), and phenylethanolamine-N-methyltransferase(PNMT) were examined in the adjacent sections of the substantia nigra & ventral tegmentum of the Striped Field Mouse(Apodemus agrarius coreae). None of these cell groups displayed either DBH or PNMT immunoreactivity. Many TH-immunoreactive neurons were present in the substantia nigra & ventral tegmentum. The major dopaminergic cell(TH-positive, DBH- & PNMT-negative) group in the midbrain was present in the pars compacta of substantia nigra and adjacent ventral tegmentum. And smaller dopaminergic cell groups Were found in the pars reticulata of the substantia nigra and central liner nucleus.

• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.499-508
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• 1997

The distributions and morphological characteristics of neurons displaying immunoreactivity to the catecholamine synthetic enzymes, tyrosine hydroxylase(TH), dopamine-${\beta}$-hydroxylase(DBH), and phenylethanolamine-N-methyltransferase (PNMT) were examined in the adjacent sections of the olfactory bulb of the Striped Field Mouse(Apodemus agrarius coreae). None of these cell groups displayed either DBH or PNMT immunoreactivity. Many TH-immunoreactive neurons were present in the olfactory bulb. The vast majority of such cells occurred in the glomerular layer as periglomerular cells surrounding the glomeruli. Numerous addtional cells were present in the external plexiform layer, and scattered in the mitral cell layer and internal plexiform layer. Also TH-immunoreactive neurons were found in the glomerular layer and granular layer of the accessory olfactory bulb.

• Radiation Oncology Journal
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• v.37 no.1
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• pp.1-12
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• 2019

Despite recent innovation in treatment techniques and subsequently improved outcomes, the majority of glioblastoma (GBL) have relapses, especially in locoregional areas. Local re-irradiation (re-RT) has been established as a feasible option for recurrent GBL of all ages with safety, tolerability, and effectiveness both in survival and quality of life regardless of fractionation schedule. To keep adverse effects under acceptable range, cumulative dose limit in equivalent dose at 2 Gy fractions by the linear-quadratic model at α/β = 2 for normal brain tissue (EQD2) with narrow margin should be observed and single/hypofractionated re-RT should be undertaken very carefully to recurrent tumor with large volume or adjacent to the brainstem. Promising outcome of re-operation (re-Op) plus re-RT (re-Op/RT) need to be validated and result from re-RT with temozolomide/bevacizumab (TMZ/BV) or new strategy is expected. Development of new-concept prognostic scoring or risk group is required to select patients properly and make use of predictive biomarkers such as O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation that influence outcomes of re-RT, re-Op/RT, or re-RT with TMZ/BV.

• Molecules and Cells
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• v.38 no.4
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• pp.362-372
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• 2015

Setdb1, an H3-K9 specific histone methyltransferase, is associated with transcriptional silencing of euchromatic genes through chromatin modification. Functions of Setdb1 during development have been extensively studied in embryonic and mesenchymal stem cells as well as neurogenic progenitor cells. But the role of Sedtdb1 in myogenic differentiation remains unknown. In this study, we report that Setdb1 is required for myogenic potential of C2C12 myoblast cells through maintaining the expressions of MyoD and muscle-specific genes. We find that reduced Setdb1 expression in C2C12 myoblast cells severely delayed differentiation of C2C12 myoblast cells, whereas exogenous Setdb1 expression had little effect on. Gene expression profiling analysis using oligonucleotide microarray and RNA-Seq technologies demonstrated that depletion of Setdb1 results in downregulation of MyoD as well as the components of muscle fiber in proliferating C2C12 cells. In addition, exogenous expression of MyoD reversed transcriptional repression of MyoD promoter-driven luciferase reporter by Setdb1 shRNA and rescued myogenic differentiation of C2C12 myoblast cells depleted of endogenous Setdb1. Taken together, these results provide new insights into how levels of key myogenic regulators are maintained prior to induction of differentiation.

• YAKHAK HOEJI
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• v.37 no.2
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• pp.149-157
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• 1993

Protein methylase inhibitor which is a modulator of biological methylation has been purified and characterized from porcine liver soluble fraction by cell fractionation, Sephadex G25 chromatography, reverse phase HPLC, size exclusion HPLC. The results are summarized as follows. 1) The purified inhibitor shows apparent homogeneity, as judged by HPLC. 2) A molecular weight of the purified inhibitor which is composed of 18 amino acid residues is about 1,400 daltons. 3) A single absorption peak of ultraviolet spectrum was observed at 260nm. 4) The inhibitor was not inactivated by heating at $100^{\circ}C$ until 60min. and its activity was not influenced by treatment with digestive enzymes, such as trypsin, pepsin, pronase, chymotrypin, lysozyme, DNase, and RNase. 5) The purified inhibitor inhibited protein rnethylase I, II, III and phospholipid methyltransferase activities. 6) The purified inhibitor inhibited noncompetitively protein methylase II from porcine liver, spleen, and testis. 7) The $K_{i}$ values for protein methylase II from porcine liver, spleen, and testis were 300nM, 250nM, 297nM, respectively.

• Proceedings of the EASDL Conference
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• 2004.10a
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• pp.13-30
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• 2004

There are two groups of significant functional constituents in sesame seeds on the whole; one is the vegetable oils and another is the anti-oxidative compounds. However, although high amounts of major fatty acids are synthesized in sesame seeds, their composition is unfavorable because the contents of alpha- and gamma-linolenic acid, the essential fatty acids, are very low or do not produced in sesame seeds. So, to increase these fatty acids in sesame seeds, one strategy is to overexpress their genes, ${\omega}$-3 fatty acid desaturase for alpha-linolenic acid and delta-6 fatty acid desaturase for gamma-linolenid acid, in them. Another molecular target is to enhance alpha-tocopherol, vitamin E, because its content is very low in sesame seeds. The enzyme, gamma-tocopherol methyltransferase, catalyzes the conversion of gamma-tocophero to alpha-tocopherol. Overexpression of this enzyme in sesame seeds could be also a good molecular breeding target. Reduction of phytic acid is also another molecular target in sesame seeds because phosphorus pollution may be caused by its high content in sesame seeds. Accordingly, to do so, one of target enzymes could be myo-inositol 1-phosphate synthase which is a key regulatory enzyme in the pathway of phytic aicd biosyntheses. In this lecture, a molecular strategy for development of value-added sesame crop is described in association with some results of our experiments involved in the molecular characterizations of the genes mentioned above.

• Archives of Pharmacal Research
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• v.14 no.4
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• pp.290-294
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• 1991

For the determination of peripheral COMT activity, we synthesized $[2-^{14}C]-3',4'-dihydroxyacetophenone([^{14}C]-DHAP)$, a model substrate closely related to catecholamines, which cannot be attacked by monoamine oxidase. After i.v.-injection of $[^{14}C]-DHAP$ in living animals, only 3',4'-dihydroxy-acetophenone (3',4'-DHAP) and 3'-methoxy-4'-hydroxyacetophenone (3'-MHAP) were detected in blood by thin layer radio chromatography. It could be speculated that 3',4'-DHAP was primarily O-methylated by COMT, followed by subsequent conjugations. The concentration of 3',4'-DHAP, a substrate for COMT, in blood at 5 min after injection of $[^{14}C]-DHAP$, were similar in all animals. The rate of 3'-MHAP formation can be therefore used as an indicator for peripheral COMT activity. The velocity of methylation in 15 min after i.v.-administration of $[^{14}C]-DHAP$ was $0.28\;{\mu}g/ml{\cdot}min$. From these results, 3',4'-DHAP was shown to be used as an appropriate substrate to determine the COMT activity in vivo.

• Proceeding of EDISON Challenge
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• 2016.03a
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• pp.90-95
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• 2016

Heat Shock 70kDa Protein 1-Like(HSPA1L)는 Heat-shock protein70(HSP70) family에 속하는 chaperone protein으로 polypeptide folding, assembly, protein degradation 등 다양한 biological processes에 관여하고 있다. HSPA1L은 human methyltransferase-like protein 21A(METTL21A)에 의해 lysine residue에 methylation이 일어나게 되는데, 암세포에서 일반적인 HSPA1L은 주로 세포질에서 발견되는 반면 methylated HSPA1L의 경우 주로 핵에서 발견이 됨으로써 HSPA1L methylation이 암 세포 성장에 중요할 역할을 할 것이라 추측되며 anti-cancer drug target으로 주목 받고 있다. 하지만 현재 HSPA1L의 구조가 부분적으로만 밝혀져 있어 HSPA1L와 METTL21A가 어떤 residue들이 interaction 하여 binding을 하는지에 대해서 아직 밝혀 지지 않았다. 이로 인해 anti-cancer drug target으로서의 연구에 제한이 있다. 이번 연구에서는 homology modeling(Galaxy-TBM, Galaxy-refine)을 통해 HSPA1L 전체 구조를 밝혀 낸 후, HSPA1L 와 METTL21A를 protein-protein docking을 통해 binding pose 예측을 하였다. 이러한 binding pose를 protein interaction analysis하여 HSPA1L과 METTL21A binding에 관여하는 중요 residue들을 밝혀 냈다. 이러한 structural information은 methylated HSPA1L와 암 세포 성장간의 연관성, 더 나아가 anti-cancer drug 개발로 까지도 이어 질 수 있을 것이라 생각한다.