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雌激素刺激 MCF7 细胞 RNA 聚合酶 II 转录变化的生物信息学分析。

Bioinformatic analysis of changes in RNA polymerase II transcription stimulated by estradiol in MCF7 cells.

出版信息

Neoplasma. 2018;65(1):14-20. doi: 10.4149/neo_2018_161214N637.

Abstract

Estradiol (E2) is the most potent estrogen and RNA polymerase II (Pol II) regulates a great mass of gene expression. This study was designed to illustrate the mechanisms of estrogen-dependent human breast cancer (BC) through Pol II. ChIP-seq data, DNase-seq data and other sequencing data of human BC MCF-7 cells were downloaded from Gene Expression Omnibus database. Each of these datasets included one control and one E2 treated sample. Sequence alignment was performed and Pol II factor binding signal was determined. Functional enrichment analysis of particular genes was performed, along with transcription factor (TF) motif enrichment analysis. Sites with enhanced Pol II binding were identified in intergenic regions. Pol II binding sites with increased binding signal facilitated chromosome switching from a closed to an open state. A total of 59 TFs, including KLF4 (Kruppel-like factor 4), were identified. Besides, enrichment analysis revealed that protein synthesis and metabolic processes as well as cell cycle processes were highlighted. The KLF4 motif was found to be enriched and was significantly enhanced in the promoter region for Pol II binding. Cell cycle processes, protein synthesis and metabolism play critical roles in the progression of E2-stimulated BC. In addition, KLF4 may be important for the progression.

摘要

雌二醇(E2)是最强的雌激素,而 RNA 聚合酶 II(Pol II)调节着大量基因的表达。本研究旨在通过 Pol II 阐明雌激素依赖性人乳腺癌(BC)的机制。从基因表达综合数据库(Gene Expression Omnibus database)下载了人乳腺癌 MCF-7 细胞的 ChIP-seq 数据、DNase-seq 数据和其他测序数据。每个数据集都包括一个对照和一个 E2 处理的样本。进行序列比对,并确定 Pol II 因子结合信号。对特定基因进行功能富集分析,并进行转录因子(TF)基序富集分析。在基因间区识别到增强的 Pol II 结合位点。Pol II 结合信号增强的结合位点促进了染色体从关闭状态向开放状态的转变。总共鉴定出 59 个 TF,包括 KLF4(Kruppel-like factor 4)。此外,富集分析表明,蛋白质合成和代谢过程以及细胞周期过程被突出显示。KLF4 基序在 Pol II 结合的启动子区域富集并显著增强。细胞周期过程、蛋白质合成和代谢在 E2 刺激的 BC 进展中起着关键作用。此外,KLF4 可能对进展很重要。

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