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.

Author Correction: WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

WNT signaling and AHCTF1 promote oncogenic MYC expression through super-enhancer-mediated gene gating.

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.

PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription.

Transcriptionally active and inactive chromatin domains tend to segregate into separate sub-nuclear compartments to maintain stable expression patterns. However, here we uncovered an inter-chromosomal network connecting active loci enriched in circadian genes to repressed lamina-associated domains (LADs). The interactome is regulated by PARP1 and its co-factor CTCF.

Central role of PAFR signalling in ExoU-induced NF-κB activation.

ExoU is an important virulence factor in acute Pseudomonas aeruginosa infections. Here, we unveiled the mechanisms of ExoU-driven NF-κB activation by using human airway cells and mice infected with P. aeruginosa strains.

ExoU activates NF-κB and increases IL-8/KC secretion during Pseudomonas aeruginosa infection.

ExoU, a Pseudomonas aeruginosa cytotoxin injected into host cytosol by type III secretion system, exhibits a potent proinflammatory activity that leads to a marked recruitment of neutrophils to infected tissues. To evaluate the mechanisms that account for neutrophil infiltration, we investigated the effect of ExoU on IL-8 secretion and NF-κB activation. We demonstrate that ExoU increases IL-8 mRNA and protein levels in P.

ExoU modulates soluble and membrane-bound ICAM-1 in Pseudomonas aeruginosa-infected endothelial cells.

ExoU, a Pseudomonas aeruginosa cytotoxin injected via the type III secretion system into host cells, possesses eicosanoid-mediated proinflammatory properties due to its phospholipase A(2) (PLA(2)) activity. This report addressed the question whether ExoU may modulate the expression of adhesion molecules in host cells, therefore contributing to the recruitment of leukocyte into infected tissues. ExoU was shown to down-regulate membrane-bound ICAM-1 (mICAM-1) and up-regulate the release of soluble ICAM-1 (sICAM-1) from P.