以次世代定序技術為基礎之尋找蛋白質修飾化轉錄因子

Genome-wide analysis of SUMO-1 and SUMO-2/3 Binding Sites Based on Next-generation ChIP-Seq Data

鄭佳揚(Chia-Yang Cheng)

指導教授 ： 唐傳義 ； 王雯靜

國立清華大學/電機資訊學院/資訊工程學系/博士(2014年)

摘要

蛋白質轉譯後修飾是蛋白質生物合成的較後步驟。被修飾後的轉錄因子如何調控基因體、其與疾病相關性，是表觀遺傳學(epigenetics)領域的重要研究課題。利用次世代定序技術可以得到同一時間點被修飾過的多種轉錄因子如何與染色體作用，但卻無法得知被修飾的轉錄因子為何。本研究提供一分析次世代定序序列資料的平台，可預測潛在被修飾的轉錄因子為何，並且利用不同時間點序列資料比對分析，推測被修飾轉錄因子的動態變化。

關鍵字

蛋白質轉譯後修飾 ； 次世代定序 ； 表觀遺傳學

並列摘要

SUMO (small ubiquitin-related modifier) was discovered to be a reversible post-translational protein modifier. SUMOylation is a highly dynamic process and its outcomes are extremely diverse. Chromatin immunoprecipitation (ChIP) in combination with high-throughput sequencing (ChIP-seq) is being applied as a gold standard when studying the genome-wide binding sites of transcription factor (TFs). This has greatly improved our understanding of protein-DNA interactions on a genomic-wide scale. However, current ChIP-seq peak calling tools are not sufficiently sensitive and are unable to simultaneously identify post-translational modified TFs based on ChIP-seq analysis; this is largely due to the wide-spread presence of multiple modified TFs. Using SUMO modification as an example; we propose a methodology that analyses SUMO ChIP-seq patterns and predicts related TFs. Our analysis uses three peak calling tools. The fusion of these different tools increases the precision of the peak calling results. TFBS annotation method is able to predict potential SUMOylated TFs. Here, we offer a new approach that enhances ChIP-seq data analysis and allows the identification of multiple SUMOylated TF binding sites simultaneously.

並列關鍵字

SUMOylation ； ChIP-seq ； epigenetics

參考文獻

Publication List

 Chia-Yang Cheng, Pei-Ching Chang, Campbell Mel, Yi-Cheng Yang, Hung-Wei Hsu, Chia-Han Chu, Chiu-Lan Huang, Shi-Mei Lai, Clifford G Tepper and Hsing-Jien Kung: The chromatin modification by SUMO-2/3 but not SUMO-1 mediates the epigenetic silencing of key immune-related genes during Kaposi's sarcoma associated herpesvirus reactivation. BMC Genomics

 Chia-Yang Cheng, Chia-Han Chu, Fang-Rong Hsu, Chung Yi Tang, Wen-Ching Wang, Hsing-Jien Kung, Pei-Ching Chang: An improved ChIP-seq peak detection system for simultaneously identifying post-translational modified transcription factors by combinatorial fusion, using SUMOylation as an example. BMC Genomics

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