• Molecules and Cells
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• v.27 no.6
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• pp.635-640
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• 2009

Testis-derived germline stem (GS) cells can undergo reprogramming to acquire multipotency when cultured under appropriate culture conditions. These multipotent GS (mGS) cells have been known to differ from GS cells in their DNA methylation pattern. In this study, we examined the DNA methylation status of the H19 imprinting control region (ICR) in multipotent adult germline stem (maGS) cells to elucidate how epigenetic imprints are altered by culture conditions. DNA methylation was analyzed by bisulfite sequencing PCR of established maGS cells cultured in the presence of glial cell line-derived neurotrophic factor (GDNF) alone or both GDNF and leukemia inhibitory factor (LIF). The results showed that the H19 ICR in maGS cells of both groups was hypermethylated and had an androgenetic pattern similar to that of GS cells. In line with these data, the relative abundance of the Igf2 mRNA transcript was two-fold higher and that of H19 was three fold lower than in control embryonic stem cells. The androgenetic DNA methylation pattern of the H19 ICR was maintained even after 54 passages. Furthermore, differentiating maGS cells from retinoic acid-treated embryoid bodies maintained the androgenetic imprinting pattern of the H19 ICR. Taken together these data suggest that our maGS cells are epigenetically stable for the H19 gene during in vitro modifications. Further studies on the epigenetic regulation and chromatin structure of maGS cells are therefore necessary before their full potential can be utilized in regenerative medicine.

• Journal of Animal Science and Technology
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• v.54 no.3
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• pp.157-163
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• 2012

The male reproduction is precisely controlled by a number of intrinsic and extrinsic factors. These factors usually involve in expressional regulation of various molecules influencing on sperm production in the testis. A number of ways are employed to control the transcription of specific genes, including epigenetic modifications of DNA and histone molecules. DNA methylation of CpG dinucleotides is a commonly used regulatory mechanism for testicular genes associated with the fertility. Previous studies have demonstrated the infertility induced by improper DNA methylation of these genes. In the present research, we attempted to determine transcriptional expression of some of these genes in the rat testis at different postnatal ages using real-time PCR analysis. These genes include neurotrophin 3 (Ntf3), insulin-like growth factor II (Igf2), JmjC-domain-containing histone demethylase 2A 1 (Jhm2da), paired box 8 transcription factor (Pax8), small nuclear ribonucleoprotein polypeptide N (Snrpn), and 5,10-methylenetetrahydrofolate reductase (Mthfr). The expression levels of Ntf3, Igf2, and Snrpn genes were the highest at the neonatal age, followed by transient decreases at the prepubertal age. Expression of Jhm2da and Mthfr genes were continuously increased from the neonate to 1 year of age. The levels of Pax8 mRNA at the early ages were higher than those at the later ages of postnatal development. These findings suggest that expression of some fertility-associated testicular genes in the rat during postnatal period could be differentially regulated by the control of the degree of DNA methylation.

• Journal of Genetic Medicine
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• v.14 no.1
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• pp.1-7
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• 2017

Purpose: The aim of this study was to assess the diagnostic efficacy of noninvasive prenatal screening for trisomy 18 by assessing the levels of unmethylated-maspin (U-maspin) and fetal nuchal translucency (NT) thickness during the first trimester of pregnancy. Materials and Methods: A nested case-control study was conducted using maternal plasma samples collected from 65 pregnant women carrying 11 fetuses with trisomy 18 and 54 normal fetuses. We compared the U-maspin levels, NT thicknesses, or a combination of both in the first trimester between the case and control groups. Results: U-maspin levels and NT thickness were significantly elevated in the first trimester in pregnant women carrying fetuses with trisomy 18 when compared to those carrying normal fetuses (27.2 vs. 6.6 copies/mL, P<0.001 for U-maspin; 5.9 vs. 2.0 mm, P<0.001 for NT). The sensitivities of the U-maspin levels and NT thickness in prenatal screening for fetal trisomy 18 were 90.9% and 90.9%, respectively, with a specificity of 98.1%. The combined U-maspin levels and NT thickness had a sensitivity of 100% in prenatal screening for fetal trisomy 18, with a specificity of 98.1%. Conclusion: A combination of U-maspin levels and NT thickness is highly efficacious for noninvasive prenatal screening of fetal trisomy 18 in the first trimester of pregnancy.

• Development and Reproduction
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• v.27 no.4
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• pp.195-203
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• 2023

Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.495-503
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• 2008

Background: Epigenetic alterations in certain genes are now known as at least important as genetic mutation in pathogenesis of cancer. Especially abnormal hypermethylation in or near promoter region of tumor suppressor genes (TSGs) are known to result in gene silencing and loss of gene function eventually. The authors tried to search for new lung cancer-specific TSGs which have CpG islands and HpaII sites, and are thought to be involved in carcinogenesis by epigenetic mechanism. Methods: Tumor tissue and corresponding adjacent normal tissue were obtained from 10 patients who diagnosed with non small cell lung cancer (NSCLC) and underwent surgery in Konyang university hospital in 2005. Methylation profiles of promoter region of 21 genes in tumor tissue & non-tumor tissue were examined with HpaII-MspI methylation microarray (Methyl-Scan DNA chip$^{(R)}$, Genomic tree, Inc, South Korea). The rates of hypermethylation were compared in tumor and non-tumor group, and as a normal control, we obtained lung tissue from two young patients with pneumothorax during bullectomies, methylation profiles were examined in the same way. Results: Among the 21 genes, 10 genes were commonly methylated in tumor, non-tumor, and control group. The 6 genes of APC, AR, RAR-b, HTR1B, EPHA3, and CFTR, among the rest of 11 genes were not methylated in control, and more frequently hypermethylated in tumor tissue than non-tumor tissue. Conclusion: In the present study, HTR1B, EPHA3, and CFTR are suggested as possible novel TSGs of NSCLC by epigenetic mechanism.

• Vacuum Magazine
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• v.5 no.1
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• pp.13-17
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• 2018

Phase transition is not unique to solid state systems or homogeneous molecular systems but it is also observed in highly heterogeneous biological systems. Phase transition and phase separation in cells are recently being found to be central to many biological functions by temporarily and locally controlling the storage and exchange of certain proteins and RNAs. There are also clues suggesting them to be playing pivotal roles in the spatial organization of chromosomes into topological domains and its time-dependent control. Here we introduce early efforts to explain at the molecular level how the spatiotemporal organization of chromosomes are programmed and modulated by the sequence and chemical modifications of the DNA. Continuing works may provide a physical framework to understand the molecular level control of chromosome structure and dynamics that determine the epigenetic state and the fate of the cells.

• Interdisciplinary Bio Central
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• v.1 no.1
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• pp.4.1-4.7
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• 2009

Introduction: Histone modifications and DNA methylation are the major factors in epigenetic gene regulation. Especially, revealing how histone modifications are related to DNA methylation is one of the challenging problems in this field. In this paper, we address this issue and propose several plausible mechanisms for precise controlling of DNA methylation status at CpG islands. Materials and Methods: To establish the regulatory relationships, we used 38 histone modification types including H2A.Z and CTCF, and DNA methylation status at CpG islands across chromosome 6, 20, and 22 of human CD4+ T cell. We utilized Bayesian network to construct regulatory network. Results and Discussion: We found several meaningful relationships supported by previous studies. In addition, our results show that histone modifications can be clustered into several groups with different regulatory properties. Based on those findings we predicted the status of methylation level at CpG islands with high accuracy, and suggested core-regulatory network to control DNA methylation status.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.113-124
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• 2009

Aging is a multifaceted biological process that affects all organs and organ systems of the body. This review provides an up-to-date analysis of this highly exciting, rapidly changing field of science. The aging process is largely under genetic control but is highly responsive to diverse environmental influences. The genes that control aging are those that are involved with cell maintenance, cell damage and repair. The environmental factors that accelerate aging are those that influence either damage of cellular macromolecules, or interfere with their repair. Prominent among these are chronic inflammation, chronic infection, some metallic chemicals, ultraviolet light, and others that heighten oxidative stress. Other environment factors slow the aging process. Included among these agents are resveratrol and vitamin D. In addition, dietary restriction and exercise have been found to extend human lifespan. The various mechanisms whereby all these agents exert their influence on aging include epigenetic modification, chromatin maintenance, protection of telomeres, and anti-oxidant defense, among others. The complex process of aging remains under continued, intense investigation.

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.2
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• pp.266-277
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• 2014

Somatic cell nuclear transfer (SCNT) has generally demonstrated that a differentiated cell can convert into a undifferentiated or pluripotent state. In the SCNT experiment, nuclear reprogramming is induced by exposure of introduced donor nuclei to the recipient cytoplasm of matured oocytes. However, because the efficiency of SCNT still remains low, a combination of SCNT technique with the ex-ovo method may improve the normal development of SCNT embryos. Here we hypothesized that treatment of somatic cells with extracts prepared from the germinal vesicle (GV) stage Siberian sturgeon oocytes prior to their use as nuclear donor for SCNT would improve in vitro development. A reversible permeability protocol with $4{\mu}g/mL$ of digitonin for 2 min at $4^{\circ}C$ in order to deliver Siberian sturgeon oocyte extract (SOE) to porcine fetal fibroblasts (PFFs) was carried out. As results, the intensity of H3K9ac staining in PFFs following treatment of SOE for 7 h at $18^{\circ}C$ was significantly increased but the intensity of H3K9me3 staining in PFFs was significantly decreased as compared with the control (p<0.05). Additionally, the level of histone acetylation in SCNT embryos at the zygote stage was significantly increased when reconstructed using SOE-treated cells (p<0.05), similar to that of IVF embryos at the zygote stage. The number of apoptotic cells was significantly decreased and pluripotency markers (Nanog, Oct4 and Sox2) were highly expressed in the blastocyst stage of SCNT embryos reconstructed using SOE-treated cells as nuclear donor (p<0.05). And there was observed a better development to the blastocyst stage in the SOE-treated group (p<0.05). Our results suggested that pre-treatment of cells with SOE could improve epigenetic reprogramming and the quality of porcine SCNT embryos.

• Journal of Photoscience
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• v.9 no.2
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• pp.221-224
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• 2002

Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.