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Cell. 2014 Mar 13;156(6):1259-73. doi: 10.1016/j.cell.2014.01.053.

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

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  • 1Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
  • 2Biozentrum, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
  • 3Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria. Electronic address: juergen.knoblich@imba.oeaw.ac.at.

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:

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

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