轉錄因子與DNA間結合模序對應關係之研究

Mapping of Transcription Factor Binding Sites and DNA-Binding Motifs

劉凱維(Kai-Wei Liu)

指導教授 ： 歐陽彥正

國立臺灣大學/電機資訊學院/資訊工程學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.10552

摘要

轉錄因子在基因調控中扮演著重要的角色，能夠促進或抑制基因的表現。轉錄因子會與特定的DNA序列鍵結並發生作用，這個被鍵結的DNA區段稱為轉錄因子結合位置(TFBS)。然而，目前轉錄因子與基因間的互動網絡大部分仍屬未知，因此找出轉錄因子在DNA結合區上的關鍵殘基，能夠提供生化學家有用的訊息，設計實驗來確認轉錄因子與基因間的作用關係。當找出DNA結合區上的關鍵殘基後，我們就能進一步建立轉錄因子與DNA間結合模序的對應關係。而本篇論文的研究，即在於設計出一套方法達成上述的目標。這套方法是將DNA結合區類型相同的轉錄因子作TFBS的分群，接著從分群好的TFBS，在其對應DNA結合區的序列上，使用非常嚴苛的標準作多重序列排比，以找出DNA結合區上的關鍵殘基。我們也針對一些在蛋白質資料庫(PDB)中擁有三級結構資訊的轉錄因子，分析這套方法找出的關鍵殘基在物理化學上之重要性。

關鍵字

轉錄因子結合位置 ； DNA結合模序 ； PFM分群

並列摘要

Transcription factors (TFs) play an essential role in gene regulation by activating or inhibiting the expressions of the corresponding genes. The transcription factors carry out their functions by docking at a specific region in the DNA sequence, which is normally referred to as transcription factor binding site (TFBS). Since the complete network of the interactions between TFs and genes is still largely unknown, figuring out the key residues in the DNA binding domain of a TF can provide the biochemists with valuable information for design of biochemical experiments to verify the interactions between the TF and the corresponding genes. Furthermore, with the key residues in the DNA binding domain identified, we can move to establish a mapping between the DNA binding motifs and the TFBS motifs. In the study reported in this thesis, we have proposed a novel approach to achieve the objectives mentioned above. The proposed approach begins with clustering the TFBSs with the same binding type. Then, sequence alignment with a strict criterion is applied to the corresponding DNA binding domains of the TFBSs in the same cluster in order to identify the key residues in the DNA binding domains. For those TFs whose tertiary structure is present in the Protein Data Bank (PDB), we have examined the physiochemical significance of the key residues identified.

並列關鍵字

TFBS ； DNA-binding motif ； PFM clustering

參考文獻

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