SWI/SNF Complex Prevents Lineage Reversion and Induces Temporal Patterning in Neural Stem Cells
Copyright policy )SWI/SNF Complex Prevents Lineage Reversion and Induces Temporal Patterning in Neural Stem Cells
Members of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in human cancer, but how they suppress tumorigenesis is currently unclear. Here, we use Drosophila neuroblasts to demonstrate that the SWI/SNF component Osa (ARID1) prevents tumorigenesis by ensuring correct lineage progression in stem cell lineages. We show that Osa induces a transcriptional program in the transit-amplifying population that initiates temporal patterning, limits self-renewal, and prevents dedifferentiation. We identify the Prdm protein Hamlet as a key component of this program. Hamlet is directly induced by Osa and regulates the progression of progenitors through distinct transcriptional states to limit the number of transit-amplifying divisions. Our data provide a mechanistic explanation for the widespread tumor suppressor activity of SWI/SNF. Because the Hamlet homologs Evi1 and Prdm16 are frequently mutated in cancer, this mechanism could well be conserved in human stem cell lineages. PAPERCLIP:
- Austrian Academy of Sciences Austria
- University of Basel Switzerland
- INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Austria
Transcription, Genetic, Biochemistry, Genetics and Molecular Biology(all), Chromosomal Proteins, Non-Histone, Brain, Nuclear Proteins, DNA-Binding Proteins, Drosophila melanogaster, Gene Expression Regulation, Neural Stem Cells, Animals, Drosophila Proteins, Humans, Genes, Tumor Suppressor, Transcription Factors
Transcription, Genetic, Biochemistry, Genetics and Molecular Biology(all), Chromosomal Proteins, Non-Histone, Brain, Nuclear Proteins, DNA-Binding Proteins, Drosophila melanogaster, Gene Expression Regulation, Neural Stem Cells, Animals, Drosophila Proteins, Humans, Genes, Tumor Suppressor, Transcription Factors
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