曹承礎臺灣大學：資訊管理學研究所陳俊璋Chen, Chun-ChangChun-ChangChen2007-11-262018-06-292007-11-262018-06-292004http://ntur.lib.ntu.edu.tw//handle/246246/54285細胞分裂是一個很重要的生命現象，在細胞分裂的過程中，為了確保染色體能正確的複製和分離，cohesion在S phase連結姊妹染色體，一直到anaphase才消失。最近，控制cohesion的蛋白質逐漸被發現。然而，關於cohesion associated regions(CARs)的特徵卻了解不多，而且絕多數的觀察是來自於單一的CAR，而非在多數的CARs發現。 本研究利用生物資訊的方法來辨識CARs的特徵。我們透過文獻找出一些可能和CAR相關的因素，包括the intergenic regions of WC orientation, scaffold/matrix attachment regions (S/MARs), autonomously replicating sequences (ARS), palindrome, tRNA genes, yeast retrotransposons and nearby long terminal repeats (LTRs)。再利用我們提出的衡量距離方法和機率模型來探討這些因素和CARs的關聯性。 我們發現在百分之九十五的信心水準下，the intergenic regions of WC orientation, scaffold/matrix attachment regions (S/MARs), autonomously replicating sequences (ARS), palindrome和tRNA genes並不是隨機在CARs附近出現。也就是說，這些因素的確和CARs有關聯。Mitosis is a very important phenomenon of life. In the mitosis of cells, cohesion connects the newly duplicated chromosomes (sister chromatids) from the S phase to anaphase to ensure the correct splitting and distribution of the genome. Recently, many proteins that control cohesion have been discovered. However, most knowledge about the characteristics of cohesion associated regions (CARs) has been gained from experiments on individual CARs. This study seeks to identify the characteristics of CARs by means of a computational approach. We review the literature and obtain a list of potential factors that may associate with CARs, including the intergenic regions of WC orientation, scaffold/matrix attachment regions (S/MARs), autonomously replicating sequences (ARS), palindrome, tRNA genes, yeast retrotransposons and nearby long terminal repeats (LTRs). We define a distance measure and propose a probabilistic model to investigate the association of each potential factor with CARs. We find that the intergenic regions of WC orientation, palindromes, S/MARs, tRNA genes and ARS do not randomly colocalize with CARs under the 95% confidence level.謝辭 i 論文摘要 ii THESIS ABSTRACT iii Table of Contents v List of Figures ix List of Tables x Chapter 1 Introduction 1 1.1 Motivation 1 1.2 Goal and Scope 3 1.3 Organization 4 Chapter 2 Background and Literature Review 5 2.1 Phases of the Cell Cycle 5 2.1.1 Interphase 6 2.1.2 Mitosis (M phase) 7 2.1.3 DNA Replication 8 2.2 The Hierarchical Level of Chromosome Organization 9 2.3 The Molecular Basics of Sister Chromatid Cohesion 10 2.3.1 The Cohesin Complex 10 2.3.2 Loading Cohesin onto Chromosomes 11 2.3.3 Establishing Cohesion during DNA Replication 11 2.4 Association of CARs to Chromosomal Features 12 2.4.1 S/MARs 12 2.4.2 Autonomously Replicating Sequence (ARS) Elements 14 2.4.3 DNA Unwinding Elements (DUEs) 16 2.4.4 Heterochromatin Barriers 16 2.4.5 Intergenic Region and Its Orientation 20 2.5 Summary 22 Chapter 3 Method and Results 23 3.1 Method 23 3.1.1 Distance Measure 24 3.1.2 A Probabilistic Model 24 3.2 Data Set 27 3.2.1 Cohesin Bound DNA from Blat and Kleckner’s Lab 27 3.2.2 Cohesin Bound DNA Used in This Study 27 3.2.3 Data Source of Potential Cis Acting Factors of CARs 29 3.3 Gene Orientation 30 3.3.1 Data 30 3.3.3 Method and Results 30 3.3.4 Discussion 32 3.4 Palindrome 36 3.4.1 Data 36 3.4.2 Method and Results 36 3.5 S/MARs 40 3.5.1 Data 40 3.5.2 Method and Results 41 3.6 tRNA Genes and Ty Elements (including LTRs) 44 3.6.1 Data 44 3.6.2 Method and Results 45 3.7 ARS 47 3.7.1 Data 47 3.7.2 Method and Results 47 3.8 Discussion 49 3.8.1 Palindrome 49 3.8.2 S/MARs 49 3.8.3 tRNA genes and LTRs 50 3.8.4 ARS 51 3.9 Summary 51 Chapter 4 Conclusions and Future Work 52 Bibliography 54 Appendix 581030713 bytesapplication/pdfen-US凝聚 (Cohesion)自主複製序列(ARS)長終端重複區(Long terminal repeats)異染色質絲(Heterochromatin)基因方向(Gene orientation)反轉序列(Palindrome)核骨架結合核醣核酸片段(S/MAR)屏障(Barriers)Long terminal repeatsScaffold/Matrix attachment regionsCohesinCohesionPalindromeBarriersGene orientationHeterochromatinAutonomously replicating sequencesotherhttp://ntur.lib.ntu.edu.tw/bitstream/246246/54285/1/ntu-93-R91725020-1.pdf