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Series GSE136451 Query DataSets for GSE136451
Status Public on Jan 17, 2020
Title WDR5 is a conserved regulator of protein synthesis gene expression
Organisms Homo sapiens; Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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. Here, we have performed comparative genomic analyses to identify the conserved sites of WDR5 binding to chromatin, and the conserved genes regulated by WDR5, across a diverse panel of cancer cell lines. We show that a specific cohort of protein synthesis genes (PSGs) are invariantly bound by WDR5, demonstrate that the WIN site anchors WDR5 to chromatin at these sites, and establish that PSGs are both acute and persistent targets of WIN site blockade. Together, these data reveal that WDR5 plays a predominant transcriptional role in biomass accumulation and reinforce the notion that WIN site inhibitors kill sensitive cancer cells by disrupting protein synthesis homeostasis.
Overall design ChIP-Seq was used to track the interaction of WDR5 with chromatin in LoVo, Be2C, MC38, and 3T3 cells. ChIP-seq in LoVo cells includes 2 IgG (control) biological replicates, and 2 WDR5 biological replicates. ChIP-seq in Be2C, MC38, and 3T3 cells includes 3 IgG (control) biological replicates and 3 WDR5 biological replicates. For RNA studies, either LoVo or CHP134 cells were treated with the WIN site inhibitor C6, or DMSO (control). SLAM-Seq was used to monitor early transcriptional changes in LoVo cells after 4 hours of treatment with DMSO or 25 uM C6 - 3 DMSO-treated biological replicates and 3 C6-treated biological replicates are included. RNA-Seq was used to monitor transcriptional changes in CHP134 cells after 24 hours of treatment with DMSO or 5 uM C6 - 3 DMSO-treated biological replicates and 3 C6-treated biological replicates are included.
Contributor(s) Tansey W, Foshage A, Weissmiller A, Wang J, Liu Q
Citation(s) 31996893, 33472061
Submission date Aug 27, 2019
Last update date Feb 16, 2021
Contact name Jing Wang
Organization name Vanderbilt University Medical Center
Street address 2220 Pierce Avenue
City Nashville
State/province TN
ZIP/Postal code 37232
Country USA
Platforms (4)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (46)
GSM4050752 LoVo ChIP-seq IgG rep1
GSM4050753 LoVo ChIP-seq IgG rep2
GSM4050754 LoVo ChIP-seq WDR5 rep1
BioProject PRJNA562551
SRA SRP219471

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE136451_CHP134-count.txt.gz 1.4 Mb (ftp)(http) TXT
GSE136451_CHP134-dTAG47-count.txt.gz 326.2 Kb (ftp)(http) TXT
GSE136451_RAW.tar 3.1 Mb (http)(custom) TAR (of CSV, NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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