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Series GSE86556 Query DataSets for GSE86556
Status Public on Apr 13, 2017
Title The 3’-UTR of MYC couples RNA polymerase II function to ribonucleotide levels
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Deregulated expression of MYC enhances glutamine utilization and renders cell survival dependent on an external supply of glutamine, an observation termed “glutamine addiction”. Surprisingly, human colon cancer cells, which express high levels of MYC due to mutations in the WNT pathway, are not glutamine-addicted but undergo a reversible cell cycle arrest upon glutamine deprivation. We show here that glutamine deprivation suppresses endogenous MYC expression via the 3’-UTR of the MYC mRNA, enabling escape from apoptosis. The glutamine-dependent metabolites that mediate this regulation are adenosine nucleotides. Glutamine deprivation causes a global reduction in promoter association of RNA Polymerase II (RNAPII) and reduces the RNAPII traveling ratio, indicative of defects in transcriptional elongation. While RNAPII function is restored by activation of MYC on most genes, restoration of elongation is imperfect and activation of MYC in the absence of glutamine enhances stalling of RNAPII in the body of individual genes, promoting the formation of R-loops. Since stalling of RNAPII and R-loop formation are potential causes of DNA damage, our data argue that the MYC 3’-UTR has a critical role in maintaining genome instability when ribonucleotide levels are low.
Overall design RNAPII binding in glutamine starved HCT116 cells and ectopic expression of MYC.
Contributor(s) Dejure FR, Royla N, Herold S, Kalb J, Walz S, Ade CP, Mastrobuoni G, Vanselow J, Schlosser A, Wolf E, Kempa S, Eilers M
Citation(s) 28408437
Submission date Sep 07, 2016
Last update date May 15, 2019
Contact name Martin Eilers
Organization name University of Wuerzburg
Department Chair for Biochemistry and Molecular Biology
Lab Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (9)
GSM2305573 EV_plusQ_input
GSM2305574 EV_plusQ_Pol2
GSM2305575 EV_plusQ_Pol2pSer2
BioProject PRJNA342303
SRA SRP087630

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Supplementary file Size Download File type/resource
GSE86556_RAW.tar 861.2 Mb (http)(custom) TAR (of BEDGRAPH)
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Raw data are available in SRA
Processed data provided as supplementary file

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