GEO DataSets

(Submitter supplied) The WIN site of WDR5 is a druggable pocket that is crucial for WDR5 protein function and carries therapeutic potential for treating cancer. This study evaluates the protein interactions affected by small molecule blockade of the WIN site of WDR5. We find that PDPK1 directly binds the WIN site of WDR5, and we investigate this newfound interaction through proteomic, biochemical, and genomic methods.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL24676 GPL20301

20 Samples

Download data: TXT

(Submitter supplied) WDR5 is a highly-conserved nuclear protein that performs multiple scaffolding functions in the context of chromatin. WDR5 is also a promising target for pharmacological inhibition in cancer, with small molecule inhibitors of an arginine-binding pocket of WDR5 (the "WIN" site) showing efficacy against a range of cancer cell lines in vitro. Efforts to understand WDR5, or establish the mechanism of action of WIN site inhibitors, however, are stymied by its many functions in the nucleus, and a lack of knowledge of the conserved gene networks—if any—that are under its control. more...

Organism:

Homo sapiens; Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

4 related Platforms

65 Samples

Download data: CSV, NARROWPEAK, TXT

(Submitter supplied) We discovered potent small molecule inhibitors against the WIN site of WDR5. These inhibitors selectively block the proliferation of mammalian cells carrying fusions of the MLL1 oncogene. Here, we show that these inhibitors result in the rapid displacement of WDR5 from chromatin in both sensitive (MV4:11) and non-sensitive (K562) cell lines, induce early changes in the distribution of active polymerases at a subset of WDR5-bound genes, and induce global transcript changes that are consistent with induction of the tumor suppressor p53.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platforms:

GPL18573 GPL21290 GPL16791

77 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) This study demonstrates the impact of WIN site inhibitors versus WDR5 degradation on H3K4me and transcriptional processes in human Burkitt's lymphoma cells. We use RNA-seq to measure global transcript levels, ChIP-seq to map genomic H3K4me3, and PRO-seq to map genomic polymerase density and primary transcripts. Our data show that WIN site inhibition disables only a specific subset of WDR5 activity, and that H3K4me changes  induced by WDR5 depletion do not explain accompanying transcriptional responses.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platform:

GPL24676

38 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) Background: During mitosis the cell depends on proper attachment and segregation of replicated chromosomes to generate two identical progeny. In cancers defined by overexpression or dysregulation of the MYC oncogene this process becomes impaired, leading to genomic instability and tumor evolution. Recently it was discovered that the chromatin regulator WDR5—a critical MYC cofactor—regulates expression of genes needed in mitosis through a direct interaction with the master kinase PDPK1. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

14 Samples

Download data: TXT

(Submitter supplied) Background: During mitosis the cell depends on proper attachment and segregation of replicated chromosomes to generate two identical progeny. In cancers defined by overexpression or dysregulation of the MYC oncogene this process becomes impaired, leading to genomic instability and tumor evolution. Recently it was discovered that the chromatin regulator WDR5—a critical MYC cofactor—regulates expression of genes needed in mitosis through a direct interaction with the master kinase PDPK1. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

4 Samples

Download data: TXT

(Submitter supplied) In this study, we utilized a multi-omics approach to determine the transcriptional, translational, and proteomic responses to WIN Site inhibition in MLL-rearranged leukemia cells via RNA-Seq, Ribo-Seq, and quantitative proteomics, respectively. We also performed both a whole-genome targeting primary CRISPR screen and a secondary CRISPR screen targeting a currated collection of genes to determine genes important for sensitivity to WIN Site inhibition. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL18573 GPL24676

56 Samples

Download data: TXT

(Submitter supplied) WD repeat domain 5 (WDR5) is a core scaffolding component of many multi-protein complexes that perform a variety of critical chromatin-centric processes in the nucleus. WDR5 is component of the mixed lineage leukemia MLL/SET complex and localizes MYC to chromatin tumor-critical target genes. Overexpression of WDR5 promotes oncogenesis in a variety of human cancers that are often associated with poor prognoses. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: TXT

(Submitter supplied) The highly conserved WD40-repeat protein WDR5 is part of multiple functional complexes both inside and outside the nucleus, interacting with the MLL/SET1 histone methyltransferases that catalyze histone H3 lysine 4 (H3K4) di- and tri-methylation (me2,3), and KIF2A, a member of the Kinesin-13 family of microtubule depolymerase. It is currently unclear whether, and how, the distribution of WDR5 between complexes is regulated. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

10 Samples

Download data: BED, BW

(Submitter supplied) We report a comparison of the genome-wide binding patterns of MYC and WDR5, and the effects of a mutation in MYC (WBM) that disrupt the MYC-WDR5 interaction.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

15 Samples

Download data: BED

(Submitter supplied) To explore the molecular mechanism underlying OICR-9429-induced WDR5 inhibition in BCa cells, a genome-wide RNA-sequencing was conducted to compare gene expression profiles between OICR-9429 treated T24, UM-UC-3 cells and their control cells

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

4 Samples

Download data: XLSX

(Submitter supplied) Rhabdoid tumors (RT) are rare and aggressive pediatric tumors that are driven by the loss the tumor suppressor SNF5 (SMARCB1). Here we examine how RT cells respond to small molecule-mediated inhibitors of the “WIN” site of WDR5, a chromatin-associated protein that regulates a specific set of genes linked to protein synthesis. We characterize WDR5 binding in RT cell lines via ChIP-Seq and show that WIN site inhibitor rapidly and comprehensively displaces WDR5 from chromatin in these cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

24 Samples

Download data: TXT

(Submitter supplied) Rhabdoid tumors (RT) are rare and aggressive pediatric tumors that are driven by the loss the tumor suppressor SNF5 (SMARCB1). Here we examine how RT cells respond to small molecule-mediated inhibitors of the “WIN” site of WDR5, a chromatin-associated protein that regulates a specific set of genes linked to protein synthesis. We characterize WDR5 binding in RT cell lines via ChIP-Seq and show that WIN site inhibitor rapidly and comprehensively displaces WDR5 from chromatin in these cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

68 Samples

Download data: TXT

(Submitter supplied) The oncoprotein transcription factor MYC is overexpressed in the majority of human cancers. Key to its oncogenic activity is the ability of MYC to bind chromatin and regulate broad gene expression patterns that drive and maintain the tumorigenic state. The interaction of MYC with chromatin is absolutely dependent on interaction with MAX, but may also be facilitated by additional chromatin-resident proteins such as WDR5. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platforms:

GPL18573 GPL20301

42 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL17021

12 Samples

Download data: BIGWIG, TXT

(Submitter supplied) Two orthotopic pancreatic tumor mouse models were used for ChIP-Seq and RNA-Seq to identify genome-wide dysfunction of H3K4me3 and gene expression. Mouse pancreatic tumors have a genome-wide increase in H3K4me3 deposition as compared to normal pancreas. Osteopontin (OPN) and its receptor CD44 were identified being up-regulated in pancreatic tumors by their promoter H3K4me3 deposition. OPN protein is increased in both tumor cells and tumor-infiltrating immune cells in human pancreatic carcinoma and is inversely correlated with pancreatic cancer patient survival. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: CSV, TXT

(Submitter supplied) Total RNA was isolated from normal C57BL/6 mouse pancreas, PANC02-H7, and UN-KC-6141 tumors from tumor-bearing mice. The RNA was used for RNA-Seq. The gene expression profiles between normal mouse pancreas and orthotopic pancreatic tumors were compared, and differentially expressed genes were identified.

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: BIGWIG

(Submitter supplied) WD repeat domain 5 (WDR5), a chromatin regulator associated with MLL complex and MYC oncoproteins, was shown to be critical for oncogenesis in human cancers and represents an attractive drug target. Inhibitors for targeting protein-protein interaction interfaces (PPIs) within WDR5 were developed; however, they inhibited only a part of WDR5-mediated functional interactions, exerting rather limited antitumor effects. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL21290

4 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Drosophila melanogaster; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

4 related Platforms

22 Samples

Download data: BW

(Submitter supplied) WD repeat domain 5 (WDR5), a chromatin regulator associated with MLL complex and MYC oncoproteins, was shown to be critical for oncogenesis in human cancers and represents an attractive drug target. Inhibitors for targeting protein-protein interaction interfaces (PPIs) within WDR5 were developed; however, they inhibited only a part of WDR5-mediated functional interactions, exerting rather limited antitumor effects. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL24676

12 Samples

Download data: XLSX