SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.

Elif Eroglu, Thomas R Burkard, Yanrui Jiang, Nidhi Saini, Catarina C F Homem, Heinrich Reichert, Juergen A Knoblich

Cell 2014 Mar 13

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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: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Elif Eroglu, Thomas R Burkard, Yanrui Jiang, Nidhi Saini, Catarina C F Homem, Heinrich Reichert, Juergen A Knoblich. SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells. Cell. 2014 Mar 13;156(6):1259-1273