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The WNT-dependent gating of MYC requires non-canonical functions of a distal CTCF binding site (RNA-Seq II)

ABSTRACT: The WNT-dependent gating of MYC requires non-canonical functions of a distal CTCF binding site (RNA-Seq II)

PROVIDER: PRJNA763186 | ENA |

REPOSITORIES: ENA

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The WNT-dependent gating of MYC requires non-canonical functions of a distal CTCF binding site

Project description:Abnormal WNT signaling increases MYC expression in colon cancer cells in part via oncogenic super-enhancer (OSE)-mediated gating of MYC to the nuclear pore. This process enables MYC transcripts to escape the higher degradation rate in the nucleus compared to the cytoplasm. By targeted mutation, we show here that a single OSE-specific CTCF binding site (CTCFBS) mediates the WNT-regulated increased nuclear export rate of mRNAs derived from its interacting MYC and FAM49B loci, located >0.5 and >2.6 mbp distal of the OSE. The CTCFBS coordinated OSE-MYC proximity with their peripheral localisation, and mediated the WNT-dependent recruitment of the nuclear pore anchor AHCTF1 to the OSE. Furthermore, the CTCFBS up-regulated CCAT1 eRNA transcription, implicated in OSE-MYC interactions, correlating with an enhanced ability of the OSE to reach the nuclear periphery. We submit that WNT-dependent gating of MYC requires CTCF complexed with the OSE to coordinate multiple steps of the gating process.

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

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