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| Status |
Public on Oct 03, 2023 |
| Title |
CCG-1423-derived compounds reduce global RNA synthesis and inhibit transcriptional responses (PRO-seq) |
| Organism |
Drosophila melanogaster |
| Experiment type |
Other
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| Summary |
Myocardin-related transcription factors (MRTFs) are coactivators of serum response factor (SRF), and thereby regulate cytoskeletal gene expression in response to actin dynamics. MRTFs have also been implicated in heat shock protein (hsp) transcription in fly ovaries, but the mechanisms remain unclear. Here we demonstrate that in mammalian cells, MRTFs are dispensable for hsp gene induction. However, the widely used small molecule inhibitors of MRTF/SRF transcription pathway, derived from CCG-1423, efficiently inhibit hsp gene transcription in both fly and mammalian cells also in absence of MRTFs. Quantifying RNA synthesis and RNA polymerase distribution demonstrates that CCG-1423-derived compounds have a genome-wide effect on transcription. Indeed, tracking nascent transcription at nucleotide resolution reveals that CCG-1423-derived compounds reduce RNA polymerase II elongation, and severely dampen the transcriptional response to heat shock. The effects of CCG-1423-derived compounds therefore extend beyond the MRTF/SRF pathway into nascent transcription, opening novel opportunities for their use in transcription research.
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| Overall design |
2 replicates of PRO-seq was performed in S2R+ cells. Drug treatment was done for allocated timepoints (10 mins with the inhibitors at NH condition) followed by heat shock for 20 mins in 37°C waterbath.
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| Contributor(s) |
Vihervaara A, Sokolova M, Prajapati B |
| Citation missing |
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| Submission date |
Sep 28, 2023 |
| Last update date |
Oct 03, 2023 |
| Contact name |
Maria Sokolova |
| E-mail(s) |
[email protected]
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| Organization name |
University of Helsinki
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| Department |
Institute of Biotechnology
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| Lab |
Nuclear Actin Lab
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| Street address |
Viikinkaari 5
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| City |
Helsinki |
| ZIP/Postal code |
00014 |
| Country |
Finland |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (8)
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| GSM7809123 |
S2,NHS,ctrl,rep1 |
| GSM7809124 |
S2,HS,CCG-1423,rep2 |
| GSM7809125 |
S2,HS,ctrl,rep2 |
| GSM7809126 |
S2,NHS,CCG-1423,rep2 |
| GSM7809127 |
S2,NHS,ctrl,rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE244232 |
CCG-1423-derived compounds reduce global RNA synthesis and inhibit transcriptional responses |
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| Relations |
| BioProject |
PRJNA1021949 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE244231_RAW.tar |
378.0 Mb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
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