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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 20, 2024 |
| Title |
Basis of gene-specific transcription regulation by the Inegrator Complex (ChIP-Seq II) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Integrator (INT) is a multi-subunit modular RNA processing complex, which exhibits both RNA endonuclease and protein phosphatase activity. It is responsible for transcription termination at the 3’ ends of a diverse array of RNA polymerase II (RNAP2) transcribed non-coding RNAs, as well as transcription regulation at a large number of protein coding genes. There, it terminates RNAP2 at promoter proximal pausing sites, cleaves the nascent transcript and competes with elongation factors.This INT-mediated tapering of gene expression attenuates stimulus responsive genes and is essential for cell differentiation. Although INT affects transcription at varying classes of RNAs in diverse biological contexts, how it achieves specificity in a gene- and context-dependent manner has remained elusive. Using a combination of proteomics, interaction studies and structural characterization, we identified a diverse set of transcription factors (TFs) that associate directly with defined surfaces on INT. Stress conditions lead to changes in the types of TFs bound by INT, and quantitative binding studies suggest that TF affinities can be modulated by altering the phosphorylation states of specific residues in their INT-binding motifs. Integrated multi-omics data show that INT and its TF interactors regulate significantly overlapping sets of genes and indicate that these TFs recruit INT to specific genomic loci. Consistently, we find that starvation induced formation of primary cilia, which is a cellular stress response reliant on INT-mediated transcription regulation, depends on intact TF-INT binding. Taken together, our data suggest that TFs lend INT specificity to elicit targeted gene regulation as a transcriptional response in defined biological contexts.
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| Overall design |
Chromatin Immunoprecipitation followed by sequencing (ChIPseq) of INTS13 after starvation or depletion of HDGF was performed to determine whether starvation stress and/or TF relocalization or depletion are associated with INTS13 relocalization on the genome.
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| Contributor(s) |
Sabath K, Nabih A, Arnold C, Moussa R, Domjan D, Zaugg J, Jonas S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Feb 28, 2024 |
| Last update date |
Jun 20, 2024 |
| Contact name |
Stefanie Jonas |
| E-mail(s) |
stefanie.jonas@mol.biol.ethz.ch
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| Organization name |
ETH Zurich
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| Department |
Biology
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| Street address |
Otto-Stern-Weg 5
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| City |
Zürich |
| State/province |
Zürich |
| ZIP/Postal code |
8093 |
| Country |
Switzerland |
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| Platforms (2) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL34284 |
Illumina NovaSeq X Plus (Homo sapiens) |
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| Samples (16)
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| GSM8118802 |
HDGF ChIP, 24h starvation, HEK293T, Rep1 |
| GSM8118803 |
HDGF ChIP, 24h starvation, HEK293T, Rep2 |
| GSM8118804 |
INTS13 ChIP, 24h starvation, HEK293T, Rep1 |
| GSM8118805 |
INTS13 ChIP, 24h starvation, HEK293T, Rep2 |
| GSM8118806 |
ChIP input, 24h starvation, HEK293T, Rep1 |
| GSM8118807 |
ChIP input, 24h starvation, HEK293T, Rep2 |
| GSM8118808 |
INTS13 ChIP, HDGF depletion, HEK293T, Rep1 |
| GSM8118809 |
INTS13 ChIP, HDGF depletion, HEK293T, Rep2 |
| GSM8118810 |
ChIP input, HDGF depletion, HEK293T, Rep1 |
| GSM8118811 |
ChIP input, HDGF depletion, HEK293T, Rep2 |
| GSM8118812 |
HDGF ChIP, ctrl depletion, HEK293T, Rep1 |
| GSM8118813 |
HDGF ChIP, ctrl depletion, HEK293T, Rep2 |
| GSM8118814 |
INTS13 ChIP, ctrl depletion, HEK293T, Rep1 |
| GSM8118815 |
INTS13 ChIP, ctrl depletion, HEK293T, Rep2 |
| GSM8118816 |
ChIP input, control depletion, HEK293T, Rep1 |
| GSM8118817 |
ChIP input, control depletion, HEK293T, Rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE233958 |
Basis of gene-specific transcription regulation by the Inegrator Complex |
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| Relations |
| BioProject |
PRJNA1081926 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE260520_HDGF_ctrl_peaks.narrowPeak.bed.gz |
1.5 Mb |
(ftp)(http) |
BED |
| GSE260520_HDGF_starv_peaks.narrowPeak.bed.gz |
1006.2 Kb |
(ftp)(http) |
BED |
| GSE260520_INTS13_ctrl_peaks.narrowPeak.bed.gz |
458.9 Kb |
(ftp)(http) |
BED |
| GSE260520_INTS13_siHDGF_peaks.narrowPeak.bed.gz |
1.5 Mb |
(ftp)(http) |
BED |
| GSE260520_INTS13_starv_peaks.narrowPeak.bed.gz |
238.5 Kb |
(ftp)(http) |
BED |
| GSE260520_RAW.tar |
6.2 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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