Abstract
The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models. We find that loss of SNF5 phenocopies β-catenin hyperactivation and that SNF5 is essential for regulating Wnt/β-catenin pathway target expression. These data provide insight into chromatin-based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
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Chromosomal Proteins, Non-Histone / deficiency
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Chromosomal Proteins, Non-Histone / genetics*
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics*
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Gene Expression Regulation, Neoplastic
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Genes, Tumor Suppressor*
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Humans
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Medulloblastoma / genetics
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Mice
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Mice, Transgenic
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Real-Time Polymerase Chain Reaction
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Rhabdoid Tumor
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SMARCB1 Protein
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Transcription Factor 4
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Transcription Factors / deficiency
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcriptome
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Tumor Cells, Cultured
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Wnt Signaling Pathway*
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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RNA, Messenger
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SMARCB1 Protein
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SMARCB1 protein, human
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors