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

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

PROVIDER: PRJNA757124 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15569817_1.fastq.gz	Fastqsanger.gz
	SRR15569817_2.fastq.gz	Fastqsanger.gz
	SRR15569818_1.fastq.gz	Fastqsanger.gz
	SRR15569818_2.fastq.gz	Fastqsanger.gz
	SRR15569819_1.fastq.gz	Fastqsanger.gz

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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.

2021-11-08 | GSE182626 | GEO

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

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

| PRJNA763189 | ENA

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

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

| PRJNA756797 | ENA

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

Project description: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 that the principal tenet of the WNT-regulated MYC gating, facilitated nuclear export of the MYC mRNA, converged on a single CTCF binding site (CTCFBS) within the OSE to confer increased growth advantage. To achieve this, the CTCFBS directed in a stepwise manner the WNT-dependent trafficking of the entire OSE to the nuclear pore from intra-nucleoplasmic positions. Once the OSE reached a perinuclear position, triggered by CTCFBS-mediated CCAT1 eRNA activation, its final stretch (<1micrometer) to the nuclear pore required the recruitment of AHCTF1, a key nucleoporin, to the CTCFBS. Thus, a novel WNT-CTCF-eRNA circuit converges on the ability of the OSE to promote pathological cell growth by coordinating the trafficking of MYC within the 3D nuclear architecture.

2021-11-06 | GSE184106 | GEO

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

2022-08-31 | GSE182556 | GEO

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

2021-11-06 | GSE184103 | GEO

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

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

| PRJNA763186 | ENA

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

Project description: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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2017-07-12 | GSE96558 | GEO

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