BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development

Development. 2013 Mar;140(6):1272-81. doi: 10.1242/dev.087379. Epub 2013 Feb 13.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Vessels / embryology
  • Blood Vessels / metabolism
  • Body Patterning / genetics*
  • COUP Transcription Factor II / genetics*
  • COUP Transcription Factor II / metabolism
  • Cells, Cultured
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Helicases / physiology*
  • Embryo, Mammalian
  • Female
  • Gene Expression Regulation, Developmental
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / physiology
  • Humans
  • Mice
  • Mice, Transgenic
  • Neovascularization, Physiologic / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Pregnancy
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Up-Regulation / genetics
  • Veins / embryology*
  • Veins / metabolism

Substances

  • COUP Transcription Factor II
  • Nr2f2 protein, mouse
  • Nuclear Proteins
  • Transcription Factors
  • Smarca4 protein, mouse
  • DNA Helicases