Fischer, Alexander and Hernandez-Rodriguez, Benjamin and Mulet-Lazaro, Roger and Nuetzel, Margit and Hoelzl, Fabian and van Herk, Stanley and Kavelaars, Francois G. and Stanewsky, Hanna and Ackermann, Ute and Niang, Amadou H. and Diaz, Noelia and Reuschel, Edith and Strieder, Nicholas and Hernandez-Lopez, Inmaculada and Valk, Peter J. M. and Vaquerizas, Juan M. and Rehli, Michael and Delwel, Ruud and Gebhard, Claudia (2024) STAG2 mutations reshape the cohesin-structured spatial chromatin architecture to drive gene regulation in acute myeloid leukemia. CELL REPORTS, 43 (8): 114498. ISSN 2211-1247,
Full text not available from this repository. (Request a copy)Abstract
Cohesin shapes the chromatin architecture, including enhancer-promoter interactions. Its components, especially STAG2, but not its paralog STAG1, are frequently mutated in myeloid malignancies. To elucidate the underlying mechanisms of leukemogenesis, we comprehensively characterized genetic, transcriptional, and chromatin conformational changes in acute myeloid leukemia (AML) patient samples. Specific loci displayed altered cohesin occupancy, gene expression, and local chromatin activation, which were not compensated by the remaining STAG1-cohesin. These changes could be linked to disrupted spatial chromatin looping in cohesin-mutated AMLs. Complementary depletion of STAG2 or STAG1 in primary human hematopoietic progenitors (HSPCs) revealed effects resembling STAG2-mutant AML-specific changes following STAG2 knockdown, not invoked by the depletion of STAG1. STAG2-deficient HSPCs displayed impaired differentiation capacity and maintained HSPC-like gene expression. This work establishes STAG2 as a key regulator of chromatin contacts, gene expression, and differentiation in the hematopoietic system and identifies candidate target genes that may be implicated in human leukemogenesis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEMATOPOIETIC STEM; GENOMIC CLASSIFICATION; TRANSCRIPTION FACTOR; COPY NUMBER; EXPRESSION; COMPLEX; FRAMEWORK; DIFFERENTIATION; PROLIFERATION; DISCOVERY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Jan 2026 10:06 |
| Last Modified: | 26 Jan 2026 10:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64352 |
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