当前位置:科学网首页 > 小柯机器人 >详情
可变启动子的工作机制获揭示
作者:小柯机器人 发布时间:2019/9/6 14:02:23

新加坡基因组研究所Jonathan Göke研究组通过对大量癌症转录组分析,发现了可变启动子的普遍调控机制。该研究于2019年9月5日发表于国际学术期刊《细胞》。

研究人员利用来自18,468个癌症和正常样品的RNA-seq数据进行活性启动子的推断,证明可变启动子是特定背景下转录调节的主要调控者。研究者发现启动子在组织,不同癌症类型和患者中失调,影响了已知的癌症基因和新的候选基因。对于具有独立调节启动子的基因,研究证明启动子活性提供了比基因表达更准确的患者存活预测指标。该研究表明,活跃启动子的动态变化塑造了癌症转录组,为进一步探索调节机制与癌症转录异常的相互作用开辟了新的思路。

据介绍,大多数人类蛋白质编码基因受多种不同启动子的调控,这表明启动子的选择与其转录水平同样重要。然而,尽管全基因组转录的改变被认为是癌症的一个决定性特征,但可变启动子的功能仍然未知。

附:英文原文

Title: A Pan-cancer Transcriptome Analysis Reveals Pervasive Regulation through Alternative Promoters

Author: Deniz Demirciolu, Engin Cukuroglu, Martin Kindermans, Tannistha Nandi, Claudia Calabrese, Nuno A. Fonseca, André Kahles, Kjong-Van Lehmann, Oliver Stegle, Alvis Brazma, Angela N. Brooks, Gunnar Rtsch, Patrick Tan, Jonathan Göke

Issue&Volume:Volume 178 Issue 6

Abstract: Most human protein-coding genes are regulated by multiple, distinct promoters, suggesting that the choice of promoter is as important as its level of transcriptional activity. However, while a global change in transcription is recognized as a defining feature of cancer, the contribution of alternative promoters still remains largely unexplored. Here, we infer active promoters using RNA-seq data from 18,468 cancer and normal samples, demonstrating that alternative promoters are a major contributor to context-specific regulation of transcription. We find that promoters are deregulated across tissues, cancer types, and patients, affecting known cancer genes and novel candidates. For genes with independently regulated promoters, we demonstrate that promoter activity provides a more accurate predictor of patient survival than gene expression. Our study suggests that a dynamic landscape of active promoters shapes the cancer transcriptome, opening new diagnostic avenues and opportunities to further explore the interplay of regulatory mechanisms with transcriptional aberrations in cancer.

DOI: 10.1016/j.cell.2019.08.018

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30906-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/