title: Cdx2 Regulates Gene Expression through Recruitment of Brg1-associated Switch-Sucrose Non-fermentable (SWI-SNF) Chromatin Remodeling Activity.
abstract: The packaging of genomic DNA into nucleosomes creates a barrier to transcription that can be relieved through ATP-dependent chromatin remodeling via complexes such as the switch-sucrose non-fermentable (SWI-SNF) chromatin remodeling complex. The SWI-SNF complex remodels chromatin via conformational or positional changes of nucleosomes, thereby altering the access of transcriptional machinery to target genes. The SWI-SNF complex has limited ability to bind to sequence-specific elements, and, therefore, its recruitment to target loci is believed to require interaction with DNA-associated transcription factors. The Cdx family of homeodomain transcript ion factors (Cdx1, Cdx2, and Cdx4) are essential for a number of developmental programs in the mouse. Cdx1 and Cdx2 also regulate intestinal homeostasis throughout life. Although a number of Cdx target genes have been identified, the basis by which Cdx members impact their transcription is poorly understood. We have found that Cdx members interact with the SWI-SNF complex and make direct contact with Brg1, a catalytic member of SWI-SNF. Both Cdx2 and Brg1 co-occupy a number of Cdx target genes, and both factors are necessary for transcriptional regulation of such targets. Finally, Cdx2 and Brg1 occupancy occurs coincident with chromatin remodeling at some of these loci. Taken together, our findings suggest that Cdx transcription factors regulate target gene expression, in part, through recruitment of Brg1-associated SWI-SNF chromatin remodeling activity.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Thinh T
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Joanne G A
authors.initials: JGA
authors.lastname: Savory
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Travis
authors.initials: T
authors.lastname: Brooke-Bisschop
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Randy
authors.initials: R
authors.lastname: Ringuette
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Foley
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Hess
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Kirk J
authors.initials: KJ
authors.lastname: Mulatz
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Trinkle-Mulcahy
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada. Electronic address: dlohnes@uottawa.ca.
authors.forename: David
authors.initials: D
authors.lastname: Lohnes
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004265:DNA Helicases / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D060066:Protein Interaction Maps; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000071616:CDX2 Transcription Factor; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases
keywords: Brg1; Cdx; ChiP; MS; SWI-SNF; chromatin remodeling; gene expression; intestine; transcription