可變啟動子的工作機制獲揭示
作者：
小柯機器人發布時間：2019/9/6 14:02:23
新加坡基因組研究所Jonathan Göke研究組通過對大量癌症轉錄組分析，發現了可變啟動子的普遍調控機制。該研究於2019年9月5日發表於國際學術期刊《細胞》。
研究人員利用來自18,468個癌症和正常樣品的RNA-seq數據進行活性啟動子的推斷，證明可變啟動子是特定背景下轉錄調節的主要調控者。研究者發現啟動子在組織，不同癌症類型和患者中失調，影響了已知的癌症基因和新的候選基因。對於具有獨立調節啟動子的基因，研究證明啟動子活性提供了比基因表達更準確的患者存活預測指標。該研究表明，活躍啟動子的動態變化塑造了癌症轉錄組，為進一步探索調節機制與癌症轉錄異常的相互作用開闢了新的思路。
據介紹，大多數人類蛋白質編碼基因受多種不同啟動子的調控，這表明啟動子的選擇與其轉錄水平同樣重要。然而，儘管全基因組轉錄的改變被認為是癌症的一個決定性特徵，但可變啟動子的功能仍然未知。
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
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216