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染色体构象捕获揭示了与 () 转录起始位点相互作用的两个元件。

Chromosome Conformation Capture Reveals Two Elements That Interact with the () Transcription Start Site.

机构信息

Innovative Medical Forum, The F. Lukaszczyk Oncology Center, Department of Molecular Oncology and Genetics, 85-796 Bydgoszcz, Poland.

The Ludwik Rydygier Collegium Medicum, Department of Thoracic Surgery And Tumours, Nicolaus Copernicus University, 85-796 Bydgoszcz, Poland.

出版信息

Int J Mol Sci. 2019 Jan 9;20(2):242. doi: 10.3390/ijms20020242.

Abstract

The long-range control of gene expression is facilitated by chromatin looping and can be detected using chromosome conformation capture-3C. Here we focus on the chromatin architecture of the (Polypyrimidine tract binding protein 3) locus to evaluate its potential role in regulating expression of the gene. expression in prostate cancer cell lines is found significantly higher compared to skin fibroblasts using real-time PCR ( < 0.05) and digital droplet PCR ( < 0.01). Exploration of the chromatin spatial architecture of a nearly 200-kb fragment of chromosome 9 encompassing the gene identified two elements located 63 kb upstream and 48 kb downstream of , which looped specifically to the promoter. These elements contain histone acetylation patterns characteristic of open chromatin regions with active enhancers. Our results reveal for the first time that long-range chromatin interactions between the -63 kb and +48 kb loci and the promoter regulate the expression of this gene in prostate cancer cells. These interactions support an open chromatin form for the locus in cancer cells and the three-dimensional structural model proposed in this paper.

摘要

通过染色质环化作用可以实现基因表达的远程控制,并且可以使用染色体构象捕获-3C 来检测。在这里,我们专注于 (多嘧啶 tract 结合蛋白 3)基因座的染色质结构,以评估其在调节基因表达中的潜在作用。使用实时 PCR(<0.05)和数字液滴 PCR(<0.01)发现,前列腺癌细胞系中的 表达明显高于皮肤成纤维细胞。探索包含 基因的近 200-kb 片段的染色体 9 的染色质空间结构,鉴定了两个位于 基因上游 63 kb 和下游 48 kb 的元件,它们特异性地环化到 启动子。这些元件包含组蛋白乙酰化模式,其特征是具有活性增强子的开放染色质区域。我们的研究结果首次揭示了-63 kb 和+48 kb 基因座与 启动子之间的长距离染色质相互作用调节前列腺癌细胞中该基因的表达。这些相互作用支持了癌细胞中 基因座的开放染色质形式和本文提出的三维结构模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7b8/6359592/d1bde05f24c3/ijms-20-00242-g001.jpg

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