title: Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5.
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.
authors: 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Division of Hematology/Oncology, Children's Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors: E L
authors: EL
authors: Mora-Blanco
authors: Novartis Institute For Biomedical Research, Cambridge, MA, USA.
authors: Y
authors: Y
authors: Mishina
authors: 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Division of Hematology/Oncology, Children's Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors: E J
authors: EJ
authors: Tillman
authors: Department of Neurology, Children's Hospital Boston, Boston, MA, USA.
authors: Y-J
authors: YJ
authors: Cho
authors: 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Division of Hematology/Oncology, Children's Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors: C S
authors: CS
authors: Thom
authors: Department of Neurology, Children's Hospital Boston, Boston, MA, USA.
authors: S L
authors: SL
authors: Pomeroy
authors: Novartis Institute For Biomedical Research, Cambridge, MA, USA.
authors: W
authors: W
authors: Shao
authors: 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Division of Hematology/Oncology, Children's Hospital Boston, Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors: C W M
authors: CW
authors: Roberts
mesh_terms: D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018335:Rhabdoid Tumor; D000071796:SMARCB1 Protein; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D060449:Wnt Signaling Pathway
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors