title: SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells.
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:
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Elif
authors.initials: E
authors.lastname: Eroglu
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Burkard
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Saini
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria.
authors.forename: Catarina C F
authors.initials: CCF
authors.lastname: Homem
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Reichert
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr-Gasse 3, 1030 Vienna, Austria. Electronic address: juergen.knoblich@imba.oeaw.ac.at.
authors.forename: Juergen A
authors.initials: JA
authors.lastname: Knoblich
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C464822:HAM protein, Drosophila; D009687:Nuclear Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C117995:osa protein, Drosophila