MYCN gene amplification in neuroblastoma drives a gene expression program that correlates strongly with aggressive disease. Mechanistically, trimethylation of histone H3 lysine 4 (H3K4) at target gene promoters is a strict pre-requisite for this transcriptional program to be enacted. WDR5 is a histone H3K4 presenter that has been found to have an essential role in H3K4 trimethylation. For this reason, in this study we investigated the relationship between WDR5-mediated H3K4 trimethylation and N-Myc transcriptional programs in neuroblastoma cells. N-Myc up-regulated WDR5 expression in neuroblastoma cells. Gene expression analysis revealed that WDR5 target genes included those with MYC binding elements at promoters such as MDM2. We showed that WDR5 could form a protein complex at the MDM2 promoter with N-Myc, but not p53, leading to histone H3K4 trimethylation and activation of MDM2 transcription. RNAi-mediated attenuation of WDR5 up-regulated expression of wild type but not mutant p53, an effect associated with growth inhibition and apoptosis. Similarly, a small molecule antagonist of WDR5 reduced N-Myc/WDR5 complex formation, N-Myc target gene expression and cell growth in neuroblastoma cells. In MYCN-transgenic mice, WDR5 was over-expressed in precancerous ganglion and neuroblastoma cells compared with normal ganglion cells. Clinically, elevated levels of WDR5 in neuroblastoma specimens were an independent predictor of poor overall survival. Overall, our results identify WDR5 as a key cofactor for N-Myc-regulated transcriptional activation and tumorigenesis and as a novel therapeutic target for MYCN-amplified neuroblastomas.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Other
4
7%
Unknown
16
27%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 July 2026.
All research outputs
#5,993,788
of 34,350,842 outputs
Outputs from Cancer Research
#9,961
of 35,807 outputs
Outputs of similar age
#72,473
of 444,719 outputs
Outputs of similar age from Cancer Research
#68
of 164 outputs
Altmetric has tracked 34,350,842 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 35,807 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.7. This one has gotten more attention than average, scoring higher than 72% of its peers.
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We're also able to compare this research output to 164 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.
