MYC基因通過超級增強子實現高效出核
作者：
小柯機器人發布時間：2019/12/2 13:31:31
瑞典卡羅林斯卡大學醫院Rolf Ohlsson、Anita Göndör等研究人員合作發現，WNT信號和AHCTF1通過超增強子介導的基因門控促進致癌MYC基因的表達。2019年11月29日，《自然—遺傳學》雜誌發表了這一研究成果。
WNT信號激活了癌細胞中MYC的表達。研究人員發現這一過程涉及致癌性超級增強子介導的活性MYC等位基因與核孔的關聯，從而增加轉錄本的輸出速率。由於MYC轉錄本在細胞核中的降解比在細胞質中更快，因此，致癌性超增強子促進的核MYC轉錄本的輸出加快了它們從結腸癌細胞的核降解系統中逃逸的速度。
在計算機建模的支持下，該過程的淨總和是結腸癌細胞中的細胞質MYC信使RNA水平高於野生型細胞。MYC的癌細胞特異性門控由AHCTF1（也稱為ELYS）調節，其通過β-catenin將核孔蛋白連接到致癌性超級增強子上。
研究人員認為，WNT信號傳導與染色質結構協作，從而在轉錄後調控經典癌症驅動因子的表達。
附：英文原文
Title: WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating
Author: Barbara A. Scholz, Noriyuki Sumida, Carolina Diettrich Mallet de Lima, Ilyas Chachoua, Mirco Martino, Ilias Tzelepis, Andrej Nikoshkov, Honglei Zhao, Rashid Mehmood, Emmanouil G. Sifakis, Deeksha Bhartiya, Anita Gndr, Rolf Ohlsson
Issue&Volume: 2019-11-29
Abstract: WNT signaling activates MYC expression in cancer cells. Here we report that this involves an oncogenic super-enhancer-mediated tethering of active MYC alleles to nuclear pores to increase transcript export rates. As the decay of MYC transcripts is more rapid in the nucleus than in the cytoplasm, the oncogenic super-enhancer-facilitated export of nuclear MYC transcripts expedites their escape from the nuclear degradation system in colon cancer cells. The net sum of this process, as supported by computer modeling, is greater cytoplasmic MYC messenger RNA levels in colon cancer cells than in wild type cells. The cancer-cell-specific gating of MYC is regulated by AHCTF1 (also known as ELYS), which connects nucleoporins to the oncogenic super-enhancer via β-catenin. We conclude that WNT signaling collaborates with chromatin architecture to post-transcriptionally dysregulate the expression of a canonical cancer driver.
DOI: 10.1038/s41588-019-0535-3
Source: https://www.nature.com/articles/s41588-019-0535-3