Wnt信号通路
CTCF公司
细胞生物学
增强子
门控
核孔蛋白
核孔
核蛋白
核定位序列
化学
核运输
生物
转录因子
细胞核
信号转导
基因
细胞质
生物化学
生物物理学
作者
Ilyas Chachoua,Ilias Tzelepis,Hao Dai,Jia Yin Lim,Anna Lewandowska-Ronnegren,Felipe Beccaria Casagrande,Shizhou Wu,Johanna Vestlund,Carolina Diettrich Mallet de Lima,Deeksha Bhartiya,Barbara A. Scholz,Mirco Martino,Rashid Mehmood,Anita Göndör
标识
DOI:10.1038/s41467-021-27868-3
摘要
Abstract Abnormal WNT signaling increases MYC expression in colon cancer cells in part via oncogenic super-enhancer-(OSE)-mediated gating of the active MYC to the nuclear pore in a poorly understood process. We show here that the principal tenet of the WNT-regulated MYC gating, facilitating nuclear export of the MYC mRNA, is regulated by a CTCF binding site (CTCFBS) within the OSE to confer growth advantage in HCT-116 cells. To achieve this, the CTCFBS directs the WNT-dependent trafficking of the OSE to the nuclear pore from intra-nucleoplasmic positions in a stepwise manner. Once the OSE reaches a peripheral position, which is triggered by a CTCFBS-mediated CCAT1 eRNA activation, its final stretch (≤0.7 μm) to the nuclear pore requires the recruitment of AHCTF1, a key nucleoporin, to the CTCFBS. Thus, a WNT/ß-catenin-AHCTF1-CTCF-eRNA circuit enables the OSE to promote pathological cell growth by coordinating the trafficking of the active MYC gene within the 3D nuclear architecture.
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