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SWI/SNF Complex Prevents Lineage Reversion and Induces Temporal Patterning in Neural Stem Cells

Eroglu, Elif and Burkard, Thomas R. and Jiang, Yanrui and Saini, Nidhi and Homem, Catarina C. F. and Reichert, Heinrich and Knoblich, Juergen A.. (2014) SWI/SNF Complex Prevents Lineage Reversion and Induces Temporal Patterning in Neural Stem Cells. Cell, Vol. 156, H. 6. pp. 1259-1273.

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Official URL: http://edoc.unibas.ch/dok/A6243473

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Abstract

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:
Faculties and Departments:05 Faculty of Science
05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Molecular Zoology (Reichert)
UniBasel Contributors:Reichert, Heinrich
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:31 Dec 2015 10:56
Deposited On:10 Oct 2014 09:19

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