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| Status |
Public on Mar 19, 2025 |
| Title |
Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia [CRISPR] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Galectin-9 is overexpressed in a variety of cancers and associated with worse clinical outcome in some cancers. However, the regulators driving Galectin-9 expression are unknown. Here, we defined the transcriptional regulators and epigenetic circuitry of Galectin-9 in pediatric T cell acute lymphoblastic leukemia (T-ALL), as an example of a disease with strong Galectin-9 expression, in which higher expression was associated with lower overall survival. By performing a genome-wide CRISPR screen, we identified the transcription factors IRF1 and TFAP4 as key regulators for Galectin-9 expression by binding its regulatory elements. While IRF1 was observed exclusively on the promoter, TFAP4 binding was detected at an enhancer solely in T-ALL cells associated with higher Galectin-9 levels. Together, our results show that IRF1 is responsible and indispensable for Galectin-9 expression and TFAP4 further fine-tunes its expression. Our approach, a flow-based genome-wide CRISPR screen complemented by transcription factor binding and enhancer mapping, creates innovative opportunities for understanding and manipulating epigenetic transcriptional regulation in cancer.
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| Overall design |
Genome-wide CRISPR screen (Brunello library) of Galectin-9 in T-ALL cell line Jurkat
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| Contributor(s) |
Wiggers CR, Yüzügüldü B, Lohr JG, Knoechel B |
| Citation missing |
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| Submission date |
Aug 16, 2024 |
| Last update date |
Mar 20, 2025 |
| Contact name |
Birgit Knoechel |
| E-mail(s) |
birgit.knoechel@hci.utah.edu
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| Organization name |
HCI
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| Street address |
2000 Circle of Hope
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| City |
Salt Lake City |
| ZIP/Postal code |
84112 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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