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| Status |
Public on May 01, 2024 |
| Title |
NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors (ATAC-Seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The pathogenesis of many rare tumor types is poorly understood, preventing the design of effective treatments. Solitary Fibrous Tumors (SFTs) are neoplasms of mesenchymal origin that affect 1/1,000,000 individuals every year and are clinically assimilated to sarcomas. SFTs are commonly found throughout the body and can be surgically removed upon diagnosis. However, 30-40% of tumors become aggressive and can locally relapse or metastasize. There are no effective treatments for malignant SFTs to date. The molecular hallmark of SFTs is a gene fusion between the NAB2 and STAT6 loci on chromosome 12, resulting in a chimeric protein of poorly characterized function called NAB2-STAT6. We use primary samples and an inducible cell model to discover that NAB2-STAT6 operates as a transcriptional coactivator for a specific set of enhancers and promoters that are normally targeted by the EGR1 transcription factor. In physiological conditions, NAB2 is primarily localized to the cytoplasm and only a small nuclear fraction is available to operate as a co-activator of EGR1 targets. NAB2-STAT6 redirects NAB1, NAB2, and additional EGR1 to the nucleus and bolster the expression of neuronal EGR1 targets. The STAT6 moiety of the fusion protein is a major driver of its nuclear localization and further contributes to NAB2’s co-activating abilities. In primary tumors, NAB2-STAT6 activates a neuroendocrine gene signature that sets it apart from most sarcomas. These discoveries provide new insight into the pathogenesis of SFTs and reveal new targets with therapeutic potential.
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| Overall design |
Omni-ATAC-seq was done in U2OS cells infected with doxycycline inducible NAB2-STAT6 expression plasmids without doxycycline treatment and after 2 days of 1ug/mL doxycycline.
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| Contributor(s) |
Hill C, Gardini A |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Dec 08, 2023 |
| Last update date |
May 01, 2024 |
| Contact name |
Alessandro Gardini |
| E-mail(s) |
agardini@wistar.org
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| Phone |
2158983755
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| Organization name |
The Wistar Institute
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| Lab |
Gardini Lab
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| Street address |
3601 Spruce St, Room 230
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| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
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| Samples (4)
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| GSM7958835 |
U2OS, pLVX-NAB2-STAT6, control, ATAC, biol rep1 |
| GSM7958836 |
U2OS, pLVX-NAB2-STAT6, control, ATAC, biol rep2 |
| GSM7958837 |
U2OS, pLVX-NAB2-STAT6, 2 days doxycycline, ATAC, biol rep1 |
| GSM7958838 |
U2OS, pLVX-NAB2-STAT6, 2 days doxycycline, ATAC, biol rep2 |
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| This SubSeries is part of SuperSeries: |
| GSE249703 |
NAB2-STAT6 drives an EGR1-dependent neuroendocrine program in Solitary Fibrous Tumors |
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| Relations |
| BioProject |
PRJNA1050213 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE249700_RAW.tar |
637.1 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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