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研究生: 陳品翰
Chen, Pin-Han
論文名稱: 建立在酵母菌中有合作關係的轉錄因子集和其調控的基因模組
Construction of a database for yeast cooperative transcription factor sets and their targeting gene modules
指導教授: 吳謂勝
Wu, Wei-Sheng
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 55
中文關鍵詞: 轉錄因子合作轉錄因子複合物轉錄調控轉錄酵母菌
外文關鍵詞: transcription factor, regulation, cooperative, complex, yeast
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  • 活細胞為了執行許多複雜的功能抵抗外在環境的變化,會透過細胞內部相互合作的轉錄因子組合成複合物調控基因表現。酵母菌的硫代謝路徑已經被生物學家研究出來,Met4活化子會結合其它轉錄因子共同合作調控硫代謝路徑中的基因,產生硫代謝路徑中需要的酶;酵母菌的呼吸作用也需要Hap2-Hap3-Hap4-Hap5複合物調控呼吸基因的表現;酵母菌可以利用多種營養源產生能量,當酵母菌使用葡萄糖作為營養源的時候,會以Mig1-Tup1-Ssn6複合物抑制參與其它代謝功能的基因表現;在酵母菌中參與細胞週期的基因是由Fkh1-Mcm1-Ndd1複合物調控。這些實際上的生物例子都說明了轉錄調控會由多個相互合作的轉錄因子一起調控基因。目前文獻中可以查詢酵母菌轉錄調控的資料庫有YEASTRACT和YCRD,YEASTRACT只能查詢單個轉錄因子調控基因資料,YCRD只能查詢合作轉錄因子對調控基因資料,因此,這兩個資料庫皆無法查詢兩個以上合作轉錄因子一起調控的基因資料,因此我們開發了一個資料庫,為了解決這個問題,我們提供二到五個合作轉錄因子一起調控目標基因的資料,幫助生物學家研究轉錄調控。我們的資料是從多個資料庫收集再經整理而來,這些資料庫有YEASTRACT、YCRD、SGD、BioGRID、YeastNet v3等;我們會將收集來的資料整理成模組資料,作為資料庫查詢使用;資料庫以人性化及容易操作的網站呈現,提供使用者查詢及瀏覽等功能搜尋我們資料庫的資料。再來我們會以酵母硫代謝路徑和酵母菌的呼吸作用等已知知識,說明我們網站的生物意義,從分析結果可以看出我們的資料庫查詢結果符合實際的轉錄調控。相信我們的資料庫將有助於生物學家進行轉錄調控的研究。我們的資料庫網址:http://cosbi4.ee.ncku.edu.tw/YGMD/。

    The regulation of gene transcription is gene activity in response to environmental change. A living cell can coordinate the activities of a set of genes by organizing the genome into gene modules. The cooperative TFs (transcription factors) which several transcription factors assemble together forming complex regulates targeting genes. Therefore, studying transcriptional regulatory modules is a useful work for elucidating cell mechanism. Nowadays, there have two databases which are YEASTRACT and YCRD can query regulatory data. YEASTRACT is a curated repository of regulatory associations between only one TF and target genes. YCRD is a repository of regulatory associations between cooperative TFs and target genes. However, only considering one TF or cooperative TFs is not enough because more than two TFs form a complex to co-regulate target genes generally. If there exist a database of regulatory associations between TFs and target genes, it may be helpful for studying transcription. That is why we construct database of regulatory associations between cooperative TFs and target genes. Our database can find target genes regulated by cooperative TFs between two and five transcription factors which have 33,024 data in our database. We provide a humanized web query function for people. It has easily operational interface and useful analysis results under search result page. Therefore, we believe that our database helps biologists to study transcriptional regulation mechanisms.

    中文摘要 I 英文摘要 III 致謝 VI 目錄 VII 表目錄 X 圖目錄 XI 第一章 研究背景與動機 1 1.1 分子生物學中心法則 1 1.2 基因表現調控機制 2 1.3 合作轉錄因子與基因模組 3 1.3.1 合作轉錄因子調控酵母菌硫代謝路徑中的基因 4 1.3.2 合作轉錄因子抑制酵母菌的分解代謝功能 6 1.3.3 合作轉錄因子調控酵母菌的呼吸作用基因 7 1.3.4 合作轉錄因子調控酵母菌細胞週期的基因 8 1.4 轉錄調控相關網站 11 1.4.1 YEASTRACT資料庫 11 1.4.2 YCRD資料庫 11 1.5 研究動機 12 1.6 論文架構 13 第二章 資料收集與處理 14 2.1 資料收集 15 2.1.1 酵母菌基因名稱及相關資料 15 2.1.2 基因集合富集分析資料 15 2.1.3 轉錄因子調控基因資料 15 2.1.4 交互作用資料 16 2.1.5 合作轉錄因子對資料 16 2.1.6 基因之間相似度關係資料 17 2.2 資料處理 18 2.2.1 酵母菌基因名稱資料處理 18 2.2.2 建構出模組資料 19 2.2.3 發展識別一群基因所含特徵的基因集合富集分析工具 23 第三章 結果與討論 25 3.1 資料庫功能介紹 25 3.1.1 搜尋頁面 26 3.1.2 瀏覽頁面 33 3.2 網站架構與功能設計 35 3.2.1 伺服器架構 35 3.2.2 網頁架構 35 3.2.3 網站功能設計 36 3.3 實例探討 43 3.3.1 合作轉錄因子調控酵母菌的硫代謝基因 43 3.3.2 合作轉錄因子調控酵母菌的呼吸作用基因 47 第四章 結論與未來展望 50 4.1 結論 50 4.2 未來展望 50 參考文獻 51

    [1] A. P. Hutchins, D. Diez, Y. Takahashi, S. Ahmad, R. Jauch, M. L. Tremblay, and D. Miranda-Saavedra. “Distinct transcriptional regulatory modules underlie STAT3’s cell type-independent and cell type-specific functions.” Nucleic acids research, vol. 41, no. 4, pp. 2155-2170, 2013.
    [2] W. S. Wu, W. H. Li, and B. S. Chen. “Computational Reconstruction of Transcriptional Regulatory Modules of the Yeast Cell Cycle.” Analysis of Microarray Data: A Network-Based Approach, vol., no., pp. 331-354, 2008.
    [3] M. Blanchette, A. R. Bataille, X. Chen, C. Poitras, J. Laganière, C. Lefèbvre, . . . D. Bergeron. “Genome-wide computational prediction of transcriptional regulatory modules reveals new insights into human gene expression.” Genome research, vol. 16, no. 5, pp. 656-668, 2006.
    [4] S. Sinha, E. Van Nimwegen, and E. D. Siggia. “A probabilistic method to detect regulatory modules.” Bioinformatics, vol. 19, no. suppl 1, pp. i292-i301, 2003.
    [5] G. Zhao, L. A. Schriefer, and G. D. Stormo. “Identification of muscle-specific regulatory modules in Caenorhabditis elegans.” Genome research, vol. 17, no. 3, pp. 348-357, 2007.
    [6] S. Hannenhalli, and S. Levy. “Transcriptional regulation of protein complexes and biological pathways.” Mammalian Genome, vol. 14, no. 9, pp. 611-619, 2003.
    [7] L. N. Singh, L.-S. Wang, and S. Hannenhalli. “TREMOR—a tool for retrieving transcriptional modules by incorporating motif covariance.” Nucleic acids research, vol. 35, no. 21, pp. 7360-7371, 2007.
    [8] D. Thomas, and Y. Surdin-Kerjan. “Metabolism of sulfur amino acids in Saccharomyces cerevisiae.” Microbiology and Molecular Biology Reviews, vol. 61, no. 4, pp. 503-532, 1997.
    [9] A. Rouillon, R. Barbey, E. E. Patton, M. Tyers, and D. Thomas. “Feedback‐regulated degradation of the transcriptional activator Met4 is triggered by the SCFMet30 complex.” The EMBO journal, vol. 19, no. 2, pp. 282-294, 2000.
    [10] S. Hohmann, and W. H. Mager. (2007). Yeast stress responses (Vol. 1): Springer Science & Business Media.
    [11] J. J. Mercado, R. Smith, F. A. Sagliocco, A. J. Brown, and J. M. Gancedo. “The levels of yeast gluconeogenic mRNAs respond to environmental factors.” European journal of biochemistry, vol. 224, no. 2, pp. 473-481, 1994.
    [12] Z. Yin, R. J. Smith, and A. J. Brown. “Multiple signalling pathways trigger the exquisite sensitivity of yeast gluconeogenic mRNAs to glucose.” Molecular microbiology, vol. 20, no. 4, pp. 751-764, 1996.
    [13] J. De Winde, and L. Grivell. “Global regulation of mitochondrial biogenesis in Saccharomyces cerevisiae.” Progress in nucleic acid research and molecular biology, vol. 46, no., pp. 51-91, 1993.
    [14] L. Grivell. “Nucleo-mitochondrial interactions in mitochondrial gene expression.” Critical Reviews in Biochemistry and Molecular Biology, vol. 30, no. 2, pp. 121-164, 1995.
    [15] Z. Hu, J. O. Nehlin, H. Ronne, and C. A. Michels. “MIG1-dependent and MIG1-independent glucose regulation of MAL gene expression in Saccharomyces cerevisiae.” Current genetics, vol. 28, no. 3, pp. 258-266, 1995.
    [16] C. Klein, L. Olsson, B. Rønnow, J. D. Mikkelsen, and J. Nielsen. “Alleviation of glucose repression of maltose metabolism by MIG1 disruption in Saccharomyces cerevisiae.” Applied and environmental microbiology, vol. 62, no. 12, pp. 4441-4449, 1996.
    [17] S. Buschlen, J. M. Amillet, B. Guiard, A. Fournier, C. Marcireau, and M. Bolotin‐Fukuhara. “The S. cerevisiae HAP complex, a key regulator of mitochondrial function, coordinates nuclear and mitochondrial gene expression.” Comparative and functional genomics, vol. 4, no. 1, pp. 37-46, 2003.
    [18] I. Simon, J. Barnett, N. Hannett, C. T. Harbison, N. J. Rinaldi, T. L. Volkert, . . . T. S. Jaakkola. “Serial regulation of transcriptional regulators in the yeast cell cycle.” Cell, vol. 106, no. 6, pp. 697-708, 2001.
    [19] N. Banerjee, and M. Q. Zhang. “Identifying cooperativity among transcription factors controlling the cell cycle in yeast.” Nucleic acids research, vol. 31, no. 23, pp. 7024-7031, 2003.
    [20] M. Elati, P. Neuvial, M. Bolotin-Fukuhara, E. Barillot, F. Radvanyi, and C. Rouveirol. “LICORN: learning cooperative regulation networks from gene expression data.” Bioinformatics, vol. 23, no. 18, pp. 2407-2414, 2007.
    [21] C. T. Harbison, D. B. Gordon, T. I. Lee, N. J. Rinaldi, K. D. Macisaac, T. W. Danford, . . . J. Yoo. “Transcriptional regulatory code of a eukaryotic genome.” Nature, vol. 431, no. 7004, pp. 99-104, 2004.
    [22] D. Datta, and H. Zhao. “Statistical methods to infer cooperative binding among transcription factors in Saccharomyces cerevisiae.” Bioinformatics, vol. 24, no. 4, pp. 545-552, 2008.
    [23] N. Nagamine, Y. Kawada, and Y. Sakakibara. “Identifying cooperative transcriptional regulations using protein–protein interactions.” Nucleic acids research, vol. 33, no. 15, pp. 4828-4837, 2005.
    [24] C.-L. Chuang, K. Hung, C.-M. Chen, and G. S. Shieh. “Uncovering transcriptional interactions via an adaptive fuzzy logic approach.” BMC bioinformatics, vol. 10, no. 1, p. 400, 2009.
    [25] H.-K. Tsai, H. H.-S. Lu, and W.-H. Li. “Statistical methods for identifying yeast cell cycle transcription factors.” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 38, pp. 13532-13537, 2005.
    [26] Y. Wang, X.-S. Zhang, and Y. Xia. “Predicting eukaryotic transcriptional cooperativity by Bayesian network integration of genome-wide data.” Nucleic acids research, vol. 37, no. 18, pp. 5943-5958, 2009.
    [27] S. Balaji, M. M. Babu, L. M. Iyer, N. M. Luscombe, and L. Aravind. “Comprehensive analysis of combinatorial regulation using the transcriptional regulatory network of yeast.” Journal of molecular biology, vol. 360, no. 1, pp. 213-227, 2006.
    [28] Y. Yang, Z. Zhang, Y. Li, X.-G. Zhu, and Q. Liu. “Identifying cooperative transcription factors by combining ChIP-chip data and knockout data.” Cell research, vol. 20, no. 11, p. 1276, 2010.
    [29] Y.-H. Chang, Y.-C. Wang, and B.-S. Chen. “Identification of transcription factor cooperativity via stochastic system model.” Bioinformatics, vol. 22, no. 18, pp. 2276-2282, 2006.
    [30] M.-J. M. Chen, L.-C. Chou, T.-T. Hsieh, D.-D. Lee, K.-W. Liu, C.-Y. Yu, . . . C.-Y. Chen. “De novo motif discovery facilitates identification of interactions between transcription factors in Saccharomyces cerevisiae.” Bioinformatics, vol. 28, no. 5, pp. 701-708, 2012.
    [31] D. He, D. Zhou, and Y. Zhou. “Identifying synergistic transcriptional factors involved in the yeast cell cycle using Microarray and ChIP-chip data.” Grid and Cooperative Computing Workshops, 2006. GCCW'06. Fifth International Conference on, vol., no., pp. 357-360, 2006.
    [32] F.-J. Lai, M.-H. Jhu, C.-C. Chiu, Y.-M. Huang, and W.-S. Wu. “Identifying cooperative transcription factors in yeast using multiple data sources.” BMC systems biology, vol. 8, no. 5, p. S2, 2014.
    [33] J. Wang. “A new framework for identifying combinatorial regulation of transcription factors: a case study of the yeast cell cycle.” Journal of biomedical informatics, vol. 40, no. 6, pp. 707-725, 2007.
    [34] W.-S. Wu, and F.-J. Lai. “Properly defining the targets of a transcription factor significantly improves the computational identification of cooperative transcription factor pairs in yeast.” BMC genomics, vol. 16, no. 12, p. S10, 2015.
    [35] X. Yu, J. Lin, T. Masuda, N. Esumi, D. J. Zack, and J. Qian. “Genome-wide prediction and characterization of interactions between transcription factors in Saccharomyces cerevisiae.” Nucleic acids research, vol. 34, no. 3, pp. 917-927, 2006.
    [36] D. S. McNabb, Y. Xing, and L. Guarente. “Cloning of yeast HAP5: a novel subunit of a heterotrimeric complex required for CCAAT binding.” Genes & Development, vol. 9, no. 1, pp. 47-58, 1995.

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