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| Status |
Public on Aug 08, 2022 |
| Title |
The bromodomain protein TRIM28 controls the balance between growth and invasiveness in melanoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Melanoma tumors are highly metastatic partly due to the ability of melanoma cells to transition between invasive and proliferative states, however, the mechanisms underlying this plasticity are still not fully understood. To identify new epigenetic regulators of melanoma plasticity, we combined data mining, tumor models, proximity proteomics, and CUT&RUN-sequencing. We focused on the druggable family of bromodomain epigenetic readers, and identified TRIM28 as a new regulator of melanoma plasticity. We found that TRIM28 promotes the expression of pro-invasive genes, and that TRIM28 controls the balance between invasiveness and growth of melanoma cells. We demonstrate that TRIM28 acts via the transcription factor JUNB, that directly regulates the expression of pro-invasive and pro-growth genes. Mechanistically, TRIM28 controls the expression of JUNB by negatively regulating its transcriptional elongation by RNA polymerase II. In conclusion, our results demonstrate that a TRIM28-JUNB axis controls the balance between invasiveness and growth in melanoma tumors and suggests that the bromodomain protein TRIM28 could be targeted to reduce tumor spread.
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| Overall design |
A375 melanoma cells were transduced with pBABE empty vector, pBABE-FOSL1 or pBABE-JUNB followed by RNA-seq to determine gene expression levels. To determine the genome binding/occupancy profiles of TRIM28 and RNA polymerase II in A375 cells we used CUT&RUN.
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| Contributor(s) |
Nyberg WA, Velasquez-Pulgarin DA, He T, Sjöstrand M, Pellé L, Covacu R, Espinosa A |
| Citation(s) |
36341538 |
| Submission date |
Aug 05, 2022 |
| Last update date |
Nov 07, 2022 |
| Contact name |
Alexander Espinosa |
| Organization name |
Karolinska Institutet
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| Department |
Dept of Medicine
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| Street address |
Visionsgatan 18
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| City |
Stockholm |
| ZIP/Postal code |
SE-17164 |
| Country |
Sweden |
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| Platforms (1) |
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| Samples (16)
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| GSM6432786 |
A375 cells transduced with empty vector pBABE retrovirus [EV_1] |
| GSM6432787 |
A375 cells transduced with empty vector pBABE retrovirus [EV_2] |
| GSM6432788 |
A375 cells transduced with empty vector pBABE retrovirus [EV_3] |
| GSM6432789 |
A375 cells transduced with empty vector pBABE retrovirus [EV_4] |
| GSM6432790 |
A375 cells transduced with pBABE-FOSL1 retrovirus [FOSL1_1] |
| GSM6432791 |
A375 cells transduced with pBABE-FOSL1 retrovirus [FOSL1_2] |
| GSM6432792 |
A375 cells transduced with pBABE-FOSL1 retrovirus [FOSL1_3] |
| GSM6432793 |
A375 cells transduced with pBABE-FOSL1 retrovirus [FOSL1_4] |
| GSM6432794 |
A375 cells transduced with pBABE-JUNB retrovirus [JUNB_1] |
| GSM6432795 |
A375 cells transduced with pBABE-JUNB retrovirus [JUNB_2] |
| GSM6432796 |
A375 cells transduced with pBABE-JUNB retrovirus [JUNB_3] |
| GSM6432797 |
A375 cells transduced with pBABE-JUNB retrovirus [JUNB_4] |
| GSM6432798 |
CUT&RUN sequencing of A375 cells (IgG control antibody) [IgG] |
| GSM6432799 |
CUT&RUN sequencing of A375 cells (TRIM28 antibody) [TRIM28] |
| GSM6432800 |
CUT&RUN sequencing of scrambled control A375 cells (RNA pol II antibody) [RNAPII_shSCR] |
| GSM6432801 |
CUT&RUN sequencing of TRIM28 knockdown A375 cells (RNA pol II antibody) [RNAPII_shT28] |
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| Relations |
| BioProject |
PRJNA866358 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE210579_Nyberg_DESeq2_normalized.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| GSE210579_RAW.tar |
1.3 Gb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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