• Title/Summary/Keyword: chromatin remodeling

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Epigenetic modification is linked to Alzheimer's disease: is it a maker or a marker?

  • Lee, Jung-Hee;Ryu, Hoon
    • BMB Reports
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    • v.43 no.10
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    • pp.649-655
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    • 2010
  • Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid $\beta$ protein (A$\beta$), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD.

Effect of Activation Time on the Nuclear Remodeling and In Vitro Development of Nuclear Transfer Embryos Derived from Bovine Somatic Cells

  • Choi, J. Y.;J. W. Cho;D. J. Kwon;Park, C. K.;B. K. Yang;Kim, C. I.;H. T. Cheong
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.6-6
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    • 2002
  • This study was conducted to investigate the effect of recipient activation time on the nuclear remodeling, chromatin structure, pronuclear formation and in vitro development of bovine nuclear transfer embryos derived from adult ear skin cells. Somatic cells were transferred to enucleated oocytes after quiescent treatments by serum starvation or culture to confluency. Nuclear transfer embryos were activated with a combination of Ca/sup 2+/-ionophore and cycloheximide at 1, 1.5, 2, 2.5, 3, and 5 h after electrofusion. (omitted)

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Nuclear and Microtubule Reorganization in Cattle Nuclear Transfered Embryos

  • Shin, Mi-Ra;Park, Sang-Wook;Cui, Xiang-Shun;Shim, Ho-Sup;Kim, Nam-Hyung
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.18-18
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    • 2001
  • Despite of importance of integrated events of nucleus and microtubule remodeling in nuclear transferred embryos with somatic cells, little information is available on this subject. In this study we configured chromatin and microtubule organization following somatic cell nuclear transfer in pre- and non-activated bovine oocytes in order to clearify nuclear remodeling process and to demonstrate centrosome inheritance during nuclear transfer. The cumulus-oocyte complexes were collected from slaughterhouse and were matured in vitro for 20 h in TCM 199 supplemented hormone. Matured bovine oocytes were enucleated by aspirating the frist polar body and metaphase chromatin using a beveled pipette. Bovine fibroblast cells were fused into enucleated oocyte by electrical stimulation. Reconstructed oocytes were activated with ionomycine and 6-dimethylaminopurin, and then cultured in CRlaa medium. The organization of nuclear and microtubules were observed using laser-scanning confocal microscopy. At 1 hour after fusion, microtubule aster was seen near the transferred nucleus in most oocytes regardless activation condition. While most of fibroblast nuclei remodeled to premature chromosome condensation (PCC) and to the two masses of chromosome in non-activated oocytes, a few number of fibloblasts went to PCC and multiple pronuclear like structures in activated oocytes. Microtubular spindle was seen around condensed chromosome. Gamma-tubulin was detected in the vicinity of condensed chromosome, suggesting this is a transient spindle. The spindle seperated nucleus into two masses of chromatin which developed to the pronuclear like structures. Two pronuclear like structures were than apposed by microtubular aster and formed one syngamy like nuclear structure at 15 h following nuclear transfer. At 17 to 18 h after fusion, two centrosomes were seen near the nucleus, which nucleates micrtubules for two cell cleavage. While 31% of reconstructed oocytes in non-activated condition developed to morulae and blastocysts, a few reconstructed oocytes in pre-activated condition developed to the blastocyst. These results suggested introduction of foreign centrosome during nuclear transfer, which appeared to give an important role for somatic cell nuclear reprogramming.

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Use of DNA Methylation for Cancer Detection and Molecular Classification

  • Zhu, Jingde;Yao, Xuebiao
    • 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.

Effect of Quiescent Treatment on Nuclear Remodeling and In Vitro Development of Nuclear Transfer Embryos Derived from Bovine Fetal Fibroblast Cells (세포의 휴면처리가 소 태아섬유아세포 유래 핵이식란의 핵상변화와 체외발육에 미치는 영향)

  • 최종엽;권대진;김정익;박춘근;양부근;정희태
    • Korean Journal of Animal Reproduction
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    • v.24 no.2
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    • pp.217-222
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    • 2000
  • This study was conducted to investigate the effect of quiescent treatment of the donor cells on the nuclear remodeling and in vitro development of fetal fibroblast cell-cloned bovine embryos. Serum starved, confluent and nonquiescent cycling fetal fibroblast cells were transferred into the enucleated oocytes. About 20∼25% of nuclear transfer embryos fused with a serum starved or confluent cell extruded a polar body, which was slightly lower than that of nontreated control (36%). About 49∼51% of nuclear transfer embryos fused with a serum starved or confluent cell had a single chromatin clump, which was slightly higher than that of nontreated control (40%). The proportion of embryos with a single chromatin clump was significantly higher (P<0.01) in nuclear transfer embryos without showing a polar body (60.5%) than with a polar body (4.7%). Development rates to the blastocyst stage were 21.7% and 20.9% when serum starved and confluent cells were transferred, which were slightly higher than that of control (14.1 %). The result of this study suggests that quiescent treatment by serum starvation or growth to confluency of donor cells could increase the number of embryos with a normal chromatin structure, which results in increased in vitro development.

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Gamma ($\GAMMA$) Tubulin and Microtubule Assembly in Porcine Nuclear Transfered Embryos and Parthenotes

  • Hong, Jun-Soon;Park, Sang-Hyun;Shun, Cui-Xiang;Kim, Nam-Hyung
    • Proceedings of the KSAR Conference
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    • 2002.06a
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    • pp.51-51
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    • 2002
  • Despite of importance of integrated events of nucleus and microtubule remodeling in nuclear transferred embryos with somatic cells, little information is available on this subject. In this study we compared chromatin, r-tubulin and microtubule organization in porcine oocytes following somatic cell nuclear transfer and parthenogenetically activation in order to clarify nuclear remodeling process and to demonstrate centrosome inheritance during nuclear transfer. (omitted)

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DNA 메틸화 Code와 발생의 Epigenetics - DNA 메틸화 전이효소(Dnmt1) 발현의 Epigenetics 제어 -

  • 고응규
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.176-182
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    • 2004
  • DNA 메틸화는 chromatin의 remodeling에 관여하고 유전자의 silencing 안정화 등, epigenetics 조절기구로서 중요하다. 포유류의 몸을 구성하는 다양한 조직과 세포는 각각 고유의 DNA 메틸화 패턴을 형성하고 있는 것이 최근의 연구에서 밝혀지고 있다. 개체발생 세포의 분화에 DNA 메틸화가 중요한 역할을 하고 있는 것이다. 본 강연에서는 DNA 메틸화 시스템에 대하여 개설하고, DNA 메틸화 전이효소(Dnmt1) 발현의 epigenetics 제어에 대하여 설명한다. Dnmtl은 제lexon의 구분에 따라 만들어지는 3종류의 iso-form이 존재한다. (중략)

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Novel $\delta$-Lactam base Histone Deacetylase Inhibitors: Synthesis and Biological Evaluation I.

  • Park, Bum-Woo;Ryu, Dong-Kyu;Kim, Tae-Kyun;Park, Song-Kyu;Han, Jeong-Hwan;Han, Gyoon-Hee
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.184.1-184.1
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    • 2003
  • HDAC and HAT (histone acetyltransferase) are involved in co-regulation in chromatin remodeling and the functional regulation of gene transcription. Abnormal recruitment of HDAC is related to carcinogenesis. Thus, the identification of potent histone deacetylase (HDAC) inhibitor has been considered as very intriguing approach for development for cancer chemotherapy. More recently, anti-inflammatory activity of SAHA cytokines was reported via reduction of proinflammatory cytokinres in vitro and in vivo. (omitted)

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