| Literature DB >> 24630726 |
Elif Eroglu1, Thomas R Burkard1, Yanrui Jiang2, Nidhi Saini2, Catarina C F Homem1, Heinrich Reichert2, Juergen A Knoblich3.
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:Entities:
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Year: 2014 PMID： 24630726 DOI： 10.1016/j.cell.2014.01.053
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582