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| Status |
Public on Mar 14, 2019 |
| Title |
Global transcriptional responses to KI-MS2-008 treatment and Myc inactivation via doxycycline addition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The Myc/Max heterodimer has crucial roles in normal cellular processes such as cell proliferation, metabolism, apoptosis, and differentiation, but its activity is often deregulated in a majority of human cancers. In an effort to explore alternative modes of Myc perturbation, we identified KI-MS2-008 as a small molecule that binds Max and modulates Myc-driven transcription, and in some cellular contexts, KI-MS2-008 treatment leads to a decrease in c-Myc protein levels. As the Myc/Max heterodimer controls many cellular processes, we expected that treatment with this small molecule would cause changes in the transcriptome. We found that treatment with 10 µM KI-MS2-008 resulted in global alterations in the transcriptome, mimicking direct Myc inactivation with doxycycline in P493-6, a B cell line with a Tet-Off system for c-Myc expression. We also discovered enrichment of various Myc target gene sets in the genes downregulated in response to KI-MS2-008 treatment in P493-6 cells. This trend was also observed in ST486 cells, but not in P3HR1 cells, which were chosen as non-engineered B cell lines that were sensitive and insensitive, respectively, toward KI-MS2-008 in cell viability assays.
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| Overall design |
RNA-seq characterizing three B cell lines: P493-6 (an engineered, KI-MS2-008 sensitive cell line), ST486 (a non-engineered, KI-MS2-008 sensitive cell line), and P3HR1 (a non-engineered, KI-MS2-008 insensitive cell line). P493-6 cells were treated with 0.1 µg/mL doxycycline, 1 µM KI-MS2-008, 10 µM KI-MS2-008, or 0.4% DMSO for 45 minutes or 8 hours. ST486 cells were treated with 1 µM KI-MS2-008, 10 µM KI-MS2-008 or 0.4% DMSO for 45 minutes or 8 hours. P3HR1 cells were treated with 10 µM KI-MS2-008 or 0.4% DMSO for 8 hours. 4 replicates were performed for each condition.
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| Contributor(s) |
Chen A, Wilson RM, Butty VL, Koehler AN |
| Citation(s) |
30880155 |
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| Submission date |
Nov 21, 2017 |
| Last update date |
Jun 16, 2019 |
| Contact name |
Andrew Chen |
| E-mail(s) |
achen5@mit.edu
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| Organization name |
Massachusetts Institute of Technology
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| Department |
Biological Engineering
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| Lab |
Koehler
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| Street address |
500 Main St. Room 389
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (64)
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| Relations |
| BioProject |
PRJNA419363 |
| SRA |
SRP125403 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107222_counts_raw_cpms.txt.gz |
6.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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