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Series GSE117240 Query DataSets for GSE117240
Status Public on Jul 18, 2018
Title ATF4 couples MYC-dependent translational activity to bioenergetic demands during tumor progression
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Dysregulation of the proto-oncogene c-Myc (MYC henceforward) drives malignant progression, but also induces robust anabolic and proliferative programs leading to intrinsic stress. The mechanisms enabling adaptation to MYC-induced stress are not fully understood. We have uncovered an essential role for the transcription factor ATF4 in cell survival following MYC activation. MYC- upregulates ATF4 by activating GCN2 kinase through uncharged tRNAs. Subsequently, ATF4 co-occupies promoter regions of over 30 MYC target genes, including those regulating amino acid biosynthesis/transport and protein synthesis. ATF4 is essential for MYC-induced upregulation of the negative translational regulator and mTOR target 4E-BP1 and genetic or pharmacological inhibition of mTOR signaling rescues ATF4 deficient cells from MYC-induced stress. Acute deletion of ATF4 significantly delays MYC-driven tumor progression and increases survival in mouse models. Our results establish ATF4 as a cellular rheostat of MYC-activity, ensuring enhanced translation rates are compatible with survival and tumor progression.
 
Overall design ATF4 and MYC CHIP-seq under control and MYC-activated conditions
 
Contributor(s) Koumenis C, Tameire F
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Submission date Jul 17, 2018
Last update date Mar 26, 2019
Contact name Priyankara J Wickramasinghe
E-mail(s) priyaw@wistar.org
Phone 2154956837
Organization name The Wistar Institute
Department Bioinformatics
Lab Genomics
Street address 3601 Spruce Street
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (7)
GSM3289764 ATF4 binding in control condition, replicate 1
GSM3289765 ATF4 binding in control condition, replicate 2
GSM3289766 ATF4 binding after 8 hours of MYC activation, replicate 1
Relations
BioProject PRJNA481516
SRA SRP154188

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

Supplementary file Size Download File type/resource
GSE117240_RAW.tar 840.0 Kb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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