Canonical WNT signaling-dependent gating of MYC requires a noncanonical CTCF function at a distal binding site

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.

Ingår i:Nature communications: Springer Science and Business Media LLC13:1, s. 204-2041-1723

Av författaren/redakt...: Chachoua, I; Tzelepis, I; Dai, H; Lim, JP; Lewandowska-Ronn ...; Casagrande, FB; visa fler...; Wu, SY; Vestlund, J; De Lima, CDM; Bhartiya, D; Scholz, BA; Martino, M; Mehmood, R; Gondor, A; visa färre...

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