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Epigenetic Regulation of the Placental Fusogenic Protein, Syncytin2
No full textSyncytin 2屬於人類內生性反轉錄病毒（human endogenous retrovirus）HERV-FRD之外鞘蛋白，其專一表現在胎盤滋養層細胞中，已知syncytin 2會促進細胞滋養層細胞進行細胞融合，而形成融合滋養層，故syncytin 2在胎盤發育上扮演重要的角色。而過去研究指出，人類胚胎發育過程中，胎盤組織裡的DNA甲基化程度明顯較胚胎本體組織來的低，且最近有報導發現，syncytin家族另一個成員syncytin 1，在胎盤細胞中，syncytin 1之5’-long terminal repeat（5’-LTR）啟動子上DNA甲基化程度非常低，使得syncytin 1能表現於胎盤細胞中，因此，本篇論文想探討是否細胞能透過改變5’LTR啟動子上DNA甲基化與組蛋白修飾等後基因修飾，而達到syncytin 2表現。實驗結果顯示，胎盤細胞或組織中的syncytin 2 5’LTR上甲基化程度顯著比非胎盤細胞來的低，且5’LTR上的組蛋白修飾皆為活化態的修飾，接著再利用報導基因方式發現syncytin 2 5’LTR若甲激化會影響到其轉錄活性，但有趣的是，含DNA甲基化syncytin 2 5’LTR的報導基因送胎盤細胞中，仍具有一定的轉錄活性，這表示胎盤細胞中具有特殊分子機制可對syncytin 2 5’LTR做去甲基化的動作；接著，發現胎盤組織特定轉錄因子GCMa可調控syncytin 2表現，且在非胎盤細胞MCF-7中表現GCMa後，會促進syncytin 2 5’LTR的DNA去甲基化，故GCMa轉錄因子除了調控基因表現外，同時在syncytin 2 5''LTR啟動子的去甲基化扮演重要角色；最後發現GCMa會與thymine DNA glycosylase（TDG）之間有結合能力，而TDG過去被指出可進行DNA去甲基化的酵素，因此GCMa可能透過吸引TDG至syncytin 2 5’LTR來進行DNA去甲基化的動作。綜合以上實驗結果，證實在胎盤細胞及非胎盤細胞中，syncytin 2 5’LTR上的後基因修飾有所不同，且胎盤特殊轉錄因子GCMa可促進syncytin 2 5’LTR DNA去甲基化以及啟動syncytin 2 mRNA表現。Syncytin 2, an envelope glycoprotein encoded by the human endogenous retrovirus FRD (HERV-FRD), is specifically expressed in placental trophoblasts. It has been reported that syncytin 2 is a fusogenic protein. Therefore, syncytin 2 may play an important role in placental development by regulation of trophoblastic fusion. Previous studies have shown that the placenta exhibits lower overall DNA methylation levels than the embryo. A recent study has shown that the 5’-long terminal repeat (5’LTR) promoter of syncytin 1, which encodes the envelope protein of HERV-W, is hypomehtylated and controls syncytin 1 expression in placenta. n this study, we further investigated whether DNA methylation and histone modification control syncytin 2 expression in placenta. We demonstrated that the 5’LTR of syncytin 2 is hypomethylated and harbors active histone modification in placental cells. In luciferase reporter assay, in vitro DNA methylation inhibited the promoter activity of syncytin 2 5’LTR. Interestingly, the promoter activity of in vitro methylated syncytin 2 5’LTR could be restored in placental cells. To study the mechanism that counteracts the suppressive effect of DNA methylation on syncytin 2 5’LTR promoter in placenta, we demonstrated that placental transcription factor, GCMa, not only regulates syncytin 2 expression but also promotes DNA demethylation on syncytin 2 5’LTR. We further demonstrated that GCMa associates with TDG, an enzyme that involves in DNA demethylation process. This implies that GCMa may recruit TDG to demethylate syncytin 2 5’LTR. Overall, our results reveal an epigenetic regulation of syncytin 2 gene expression and that GCMa is a key factor for DNA demethylation of syncytin 2 promoter and transcription activation of syncytin 2.目錄………………………………………………………………….…………………I文摘要…………………………………………………….………………..……...III文摘要…………………………………………………….……………………….IV一章 緒論. 胎盤.1 人類胎盤發育…………………………………………………………….1.2 胎盤功能………………………………………………………………….3. 後基因調控.1 簡介……………………………………………………………………….4.2去氧核糖酸甲基化………………………………………………….…….4.3 DNA methyltransferases………………………………………………..5.4 去氧核糖酸去甲基化……………………………………………………7.5 組蛋白修飾………………………………………………………………8. 人類內生性反轉錄病毒.1 簡介……………………………………………………………………….9.2 syncytin…………………………………………………………………10. gcm轉錄因子………………………………………………………………...12. 研究動機……………………………………………………………………14二章 材料與方法…………………………………………………………………15三章 結果. syncytin 2 5’LTR啟動子之DNA甲基化狀態...............................................25. syncytin 2 5’LTR啟動子上組蛋白修飾.........................................................26. 核酸甲基化對syncytin 2 5’LTR轉錄活性之影響………………………….26. GCMa調控syncytin2表現並促進syncytin 2 5’LTR區域的去甲基化…..28. GCMa在細胞中會與TDG作結合…………………………………………29四章 討論…………………………………………………………………………31五章 圖表…………………………………………………………………………35六章 參考文獻……………………………………………………………………4
GCM1 Regulation of the Expression of Syncytin 2 and Its Cognate Receptor MFSD2A in human Placenta.
No full text[[sponsorship]]生物化學研究所[[note]]已出版;[SCI];有審查制度;具代表性[[note]]http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Drexel&SrcApp=hagerty_opac&KeyRecord=0006-3363&DestApp=JCR&RQ=IF_CAT_BOXPLOT[[note]]http://gateway.isiknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=RID&SrcApp=RID&DestLinkType=FullRecord&DestApp=ALL_WOS&KeyUT=00028115380001
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Study of dynamics of histone H3 variants and H3 proteolysis during mouse spermatogenesis
Get PDFSpermatogenesis is a complex differentiation process in which male gametes, known as spermatozoa, are produced from spermatogonial stem cells in the seminiferous tubules of the testis. The spermatogenesis process is typically divided into three phases: a mitotic phase, a meiotic phase and post-meiotic spermiogenesis. During mammalian spermiogenesis, haploid round spermatids undergo remarkable morphological changes and an extensive reorganization of chromatin to differentiate into mature spermatozoa. As part of the chromatin reorganization, most histones in round spermatids are replaced by transition proteins and subsequently by protamines. This histone-to-protamine exchange is required for efficient compaction of paternal genome into the sperm head and implicated in male fertility. Nonetheless, previous studies found that 1-10 % histones are still retained at specific loci, particularly at unmethylated CpG-rich promoters, in mouse and human sperm. How spermatid chromatin is reorganized genome-wide during spermiogenesis while some loci are exempted from histone eviction is still elusive.
Our previous study has shown that the residual nucleosomes in mouse sperm largely contain the histone H3 variant, H3.3. The study also revealed differential histone turnover of canonical and variant H3 in round spermatids, which may underlie the final histone composition in mature sperm. In order to determine the dynamics of H3 variants during mouse spermatogenesis, I analyze protein expression of canonical and variant H3 proteins at different stages of male germ cells by triton-acetic acid-urea gel-Western blotting. Surprisingly, I find that mouse testis-specific H3 variant (H3t), not canonical H3, is the most abundant H3 protein from spermatogonia to spermatids and that most canonical H3 is replaced by H3.3 during meiosis. I further observe that a relatively large portion of H3t is removed from chromatin during the process of histone-to-protamine exchange compared with H3.3, which is consistent with that H3.3 is the predominant H3 in residual sperm nucleosomes. Taken together, the first part of my thesis reveals important findings on chromatin composition and dynamics of histone H3 variants during mouse spermatogenesis.
In the second part of my thesis, I describe the discovery that histone H3 is cleaved at its N-terminal tail by a serine protease activity in nuclei of the late-stage mouse spermatids. Arginine 26 and lysine 27 on H3 are important to the H3 protease activity. This proteolytic cleavage of H3 tail may result in nucleosome destabilization and then contribute to nucleosome eviction during spermiogenesis. Interestingly, I find that the acetylation on H3 can prevent H3 from proteolytic cleavage in vitro and that the genome-wide distribution of H3 lysine 27 acetylation (H3K27Ac) is positively correlated to the occupancy of nucleosomes containing transcriptionally active mark in sperm, suggesting that the inhibition of H3 cleavage by acetylated lysine 27 in late-stage spermatids may lead to the nucleosome retention at specific loci in mature sperm. Overall, these findings provide novel insights into the mechanism of nucleosome eviction and retention during spermiogenesis through the regulation of H3 proteolytic cleavage
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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