探討於強化子-啟動子交互作用中之轉錄因子結合特徵

Abstract

基因轉錄受到調控因子的調控，如強化子與啟動子等。啟動子位於基因上游附近，然而強化子常位於距離基因幾千個鹼基的位置。強化子透過在三維空間中與啟動子接觸並形成染色質環來達成調控，此為強化子-啟動子交互作用。雖然此現象眾所周知，但該機制的許多相關細節仍在研究中。 這篇論文使用了六種細胞株的染色質交互作用資料，套用計算工具掃描強化子和啟動子序列上的模組，將軟體在強化子和啟動子上掃描出的模組數量與實驗驗證的結合位點比較，發現軟體掃描回報的模組數量比起已知的結合位要多出許多。 進一步去研究有交互作用和無交互作用的強化子-啟動子配對，觀察與相同啟動子配對的有交互作用及無交互作用的強化子，比較其中的結合位模組數量。使用以軟體工具掃描出的模組，在與相同的啟動子配對的情況下，檢定有交互作用和無交互作用的強化子是否具有不同的模組組成。發現了一些模組在有交互作用和無交互作用的強化子上的出現次數達到顯著差異。然而，不同的啟動子在強化子中涉及不同系列的模組，共通有的模組不常見。在多個細胞株中也有發現僅有少量的共通模組，而找到的模組有研究指出其中一些與染色質環化有關。

Gene transcription is regulated by enhancers and promoters, which are regulatory elements. Promoters are situated close to the gene on the upstream, whereas enhancers are often located at distances up to kilobases from the gene. Enhancers bring about its regulation by coming in contact with promoters in the three-dimensional space and forming a chromatin loop. This is known as enhancer-promoter interactions. While this phenomenon is well-known, the mechanism is still under research. This thesis used chromatin interaction data of six cell lines. We used computational tools to scan the motifs on enhancer and promoter sequences. We compared the number of motifs on enhancers and promoters as scanned by software with experimental binding sites, and found that the number of motifs reported by software scanning is much larger. Interacting (positive) and non-interacting (negative) enhancer-promoter pairs were further investigated to look at positive and negative enhancers interacting with the same promoter. We took the scanned motifs and tested whether positive and negative enhancers have different motif composition given that they interact with the same promoter. Some motifs were found to have significant different occurrences in positive and negative enhancers. Different promoters usually involved a different set of motifs in enhancers, and common motifs were few. There were also a few motifs that were commonly found in multiple cell lines. Among the motifs we found, some were reported to be linked to chromatin looping.