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Series GSE112379 Query DataSets for GSE112379
Status Public on Feb 07, 2019
Title Nascent-protein ubiquitination is required for heat shock-induced gene downregulation in human cells.
Organism Homo sapiens
Experiment type Other
Genome binding/occupancy profiling by high throughput sequencing
Summary Proteotoxic stress such as heat shock causes heat-shock factor (HSF)-dependent transcriptional upregulation of chaperones. Heat shock also leads to a rapid and reversible downregulation of many genes, a process we term stress-induced transcriptional attenuation (SITA). The mechanism underlying this conserved phenomenon is unknown. Here we report that enhanced recruitment of negative transcription elongation factors to gene promoters in human cell lines induces SITA. A chemical inhibitor screen showed that active translation and protein ubiquitination are required for the response. We further find that proteins translated during heat shock are subjected to ubiquitination and that p38 kinase signaling connects cytosolic translation with gene downregulation. Notably, brain samples of subjects with Huntington's disease also show transcriptional attenuation, which is recapitulated in cellular models of protein aggregation similar to heat shock. Thus our work identifies an HSF-independent mechanism that links nascent-protein ubiquitination to transcriptional downregulation during heat shock, with potential ramifications in neurodegenerative diseases.
Overall design Examination of stress-induced gene attenuation
Contributor(s) Aprile Garcia F, Tomar P, Hummel B, Sawarkar R
Citation(s) 30723328
Submission date Mar 27, 2018
Last update date Mar 27, 2019
Contact name Barbara Hummel
Organization name Max Planck Institute of Immunobiology and Epigenetics
Street address Stübeweg 51
City Freiburg
ZIP/Postal code 79108
Country Germany
Platforms (3)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (50)
GSM3068950 HEK_NHS_Proseq_Rep1
GSM3068951 HEK_NHS_Proseq_Rep2
GSM3068952 HEK_NHS_Proseq_Rep3
BioProject PRJNA445860
SRA SRP136551

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
GSE112379_DESeq2_GeneBodyCounts_ChIPseq_HEK.txt.gz 374.0 Kb (ftp)(http) TXT
GSE112379_DESeq2_GeneBodyCounts_ChIPseq_K562.txt.gz 306.7 Kb (ftp)(http) TXT
GSE112379_RAW.tar 12.4 Gb (http)(custom) TAR (of BW)
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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