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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jun 22, 2022 |
| Title |
The TFEB – TGIF1 axis regulates EMT in mouse epicardial cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGFβ/Smad pathway repressor. The Tgif1 promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression when Tfeb is overexpressed. Furthermore, Tfeb overexpression in vitro prevented TGFβ-induced EMT, and this effect was abolished by Tgif1 silencing. Tfeb loss of function, similar to that of Tgif1, sensitized cells to TGFβ, inducing an EMT response to low doses of TGFβ. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide new insights into injured heart repair and control of cancer progression.
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| Overall design |
ChIP seq of overexpressed TFEB S142A and IgG in mouse epicardial cells
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| Contributor(s) |
Astanina E, Doronzo G, Cora' D, Neri F, Oliviero S, Bussolino F |
| Citation(s) |
36057632 |
| Submission date |
Jun 21, 2021 |
| Last update date |
Sep 15, 2022 |
| Contact name |
Davide Cora' |
| E-mail(s) |
davide.cora@ircc.it, davide.cora@uniupo.it
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| Phone |
+390321660631
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| Organization name |
Piemonte Orientale University and IRCCS Candiolo Cancer Institute
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| Department |
Dept. of Oncology
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| Lab |
Vascular Oncology
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| Street address |
Str. Prov. 142 Km. 3.95
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| City |
Candiolo |
| State/province |
TO |
| ZIP/Postal code |
I-10060 |
| Country |
Italy |
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| Platforms (1) |
| GPL16173 |
Illumina HiScanSQ (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA739679 |
| SRA |
SRP324857 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE178575_RAW.tar |
140.0 Kb |
(http)(custom) |
TAR (of BED) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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