title: BRG1 interacts with GLI2 and binds Mef2c gene in a hedgehog signalling dependent manner during in vitro cardiomyogenesis.
abstract: The Hedgehog (HH) signalling pathway regulates cardiomyogenesis in vivo and in differentiating P19 embryonal carcinoma (EC) cells, a mouse embryonic stem (mES) cell model. To further assess the transcriptional role of HH signalling during cardiomyogenesis in stem cells, we studied the effects of overexpressing GLI2, a primary transducer of the HH signalling pathway, in mES cells.
  
  
  
  Stable GLI2 overexpression resulted in an enhancement of cardiac progenitor-enriched genes, Mef2c, Nkx2-5, and Tbx5 during mES cell differentiation. In contrast, pharmacological blockade of the HH pathway in mES cells resulted in lower expression of these genes. Mass spectrometric analysis identified the chromatin remodelling factor BRG1 as a protein which co-immunoprecipitates with GLI2 in differentiating mES cells. We then determined that BRG1 is recruited to a GLI2-specific Mef2c gene element in a HH signalling-dependent manner during cardiomyogenesis in P19 EC cells, a mES cell model.
  
  
  
  Thus, we propose a mechanism where HH/GLI2 regulates the expression of Mef2c by recruiting BRG1 to the Mef2c gene, most probably via chromatin remodelling, to ultimately regulate in vitro cardiomyogenesis.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada.
authors.forename: Joel Vincent
authors.initials: JV
authors.lastname: Fair
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Voronova
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada.
authors.forename: Neven
authors.initials: N
authors.lastname: Bosiljcic
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada.
authors.forename: Rashida
authors.initials: R
authors.lastname: Rajgara
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada. alexandre.blais@uottawa.ca.|Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada. alexandre.blais@uottawa.ca.
authors.forename: Alexandre
authors.identifier: 0000-0003-2446-1883
authors.initials: A
authors.lastname: Blais
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, K1H 8M5, Ottawa, Canada. iskerjan@uottawa.ca.
authors.forename: Ilona Sylvia
authors.initials: IS
authors.lastname: Skerjanc
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000075746:Zinc Finger Protein Gli2
chemical_list: C000618551:Gli2 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D000075746:Zinc Finger Protein Gli2; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: BRG1; Cardiac development; Cardiomyogenesis; GLI2; Hedgehog signalling pathway