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| Status |
Public on Jun 20, 2024 |
| Title |
SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression (CUT＆RUN) |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor SP1 plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master transcription factors may form phase-separated macromolecular condensates to promote super-enhancer assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA binding domain is essential for this process. Through CUT&RUN using antibodies against SP1 and H3K27ac, we discovered a significant correlation between SP1 enrichment and super-enhancer elements, identified the regulator of G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through super-enhancer mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by GSK-J4, a demethylase inhibitor. Together, our findings provide the first evidence that SP1 regulates its target oncogene expression through phase separation and super-enhancer mechanisms, thereby promoting LUAD cell progression. This study also revealed a novel target for LUAD therapies through intervening in SP1-mediated super-enhancer formation.
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| Overall design |
We investigate the H3K27ac histone modification or SP1 profiles of H1299 cell lines.
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| Contributor(s) |
Shan L, Wang W |
| Citation missing |
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| Submission date |
Jun 17, 2024 |
| Last update date |
Jun 21, 2024 |
| Contact name |
Fang Liu |
| E-mail(s) |
fangliu@hrbmu.edu.cn
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| Organization name |
Harbin Medical University
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| Street address |
Harbin health care road
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| City |
Harbin |
| ZIP/Postal code |
150081 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1124850 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE270008_RAW.tar |
769.5 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
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