瑞典卡罗林斯卡大学医院Rolf Ohlsson、Anita Göndör等研究人员合作发现，WNT信号和AHCTF1通过超增强子介导的基因门控促进致癌MYC基因的表达。2019年11月29日，《自然—遗传学》杂志发表了这一研究成果。

WNT信号激活了癌细胞中MYC的表达。研究人员发现这一过程涉及致癌性超级增强子介导的活性MYC等位基因与核孔的关联，从而增加转录本的输出速率。由于MYC转录本在细胞核中的降解比在细胞质中更快，因此，致癌性超增强子促进的核MYC转录本的输出加快了它们从结肠癌细胞的核降解系统中逃逸的速度。

在计算机建模的支持下，该过程的净总和是结肠癌细胞中的细胞质MYC信使RNA水平高于野生型细胞。MYC的癌细胞特异性门控由AHCTF1（也称为ELYS）调节，其通过β-catenin将核孔蛋白连接到致癌性超级增强子上。

研究人员认为，WNT信号传导与染色质结构协作，从而在转录后调控经典癌症驱动因子的表达。

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