 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 11, 2023 |
| Title |
PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors and transcriptional regulators converge to be regulated. Specific associations of PML and PML-NBs with chromatin are described in different cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in a cellular context where it regulates relevant phenotypes is still lacking.We examined the role of PML in chromatin association and transcription in triple-negative breast cancer (TNBC), a pathological condition where PML exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a cell type-relevant function of transcriptional regulation. PML also plays an indirect regulatory function in TBNC cells by promoting the expression of pro-metastatic genes outside PADs.Our findings demonstrate that PML is an important transcriptional regulator of metastasis and pro-oncogenic metagenes in TNBC cells, via distinct molecular activities that include indirect transcriptional regulation and direct epigenetic organization of heterochromatin domains that embed regions of localized transcriptional activity.
|
| |
|
| Overall design |
RNA-sequencing (RNA-seq) in control and PML silenced MDA-MB-231 cells.
|
| |
|
| Contributor(s) |
Fracassi C, Ugge’ M, Abdelhalim M, Zapparoli E, Lazarevic D, Morelli JM, Collas P, Bernardi R |
| Citation(s) |
37823593 |
| |
| Submission date |
Feb 25, 2023 |
| Last update date |
Dec 11, 2023 |
| Contact name |
Rosa Bernardi |
| E-mail(s) |
bernardi.rosa@hsr.it
|
| Organization name |
San Raffaele Scientific Institute
|
| Street address |
via Olgettina 60
|
| City |
Milan |
| ZIP/Postal code |
20132 |
| Country |
Italy |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (6)
|
|
| This SubSeries is part of SuperSeries: |
| GSE226210 |
PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer |
|
| Relations |
| BioProject |
PRJNA938748 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE226111_Counts_ctrl_shpml.txt.gz |
511.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...