title: BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development.
abstract: Arteries and veins acquire distinct molecular identities prior to the onset of embryonic blood circulation, and their specification is crucial for vascular development. The transcription factor COUP-TFII currently functions at the top of a signaling pathway governing venous fate. It promotes venous identity by inhibiting Notch signaling and subsequent arterialization of endothelial cells, yet nothing is known about what regulates COUP-TFII expression in veins. We now report that the chromatin-remodeling enzyme BRG1 promotes COUP-TFII expression in venous endothelial cells during murine embryonic development. Conditional deletion of Brg1 from vascular endothelial cells resulted in downregulated COUP-TFII expression and aberrant expression of arterial markers on veins. BRG1 promotes COUP-TFII expression by binding conserved regulatory elements within the COUP-TFII promoter and remodeling chromatin to make the promoter accessible to transcriptional machinery. This study provides the first description of a factor promoting COUP-TFII expression in vascular endothelium and highlights a novel role for chromatin remodeling in venous specification.
authors: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors: Reema B
authors: RB
authors: Davis
authors: Carol D
authors: CD
authors: Curtis
authors: Courtney T
authors: CT
authors: Griffin
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics*; D051837:COUP Transcription Factor II / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics; D014680:Veins / Q000196:embryology* / Q000378:metabolism
chemical_list: D051837:COUP Transcription Factor II; C497587:Nr2f2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases