SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development

Chiang, I.K., Fritzsche, M., Pichol-Thievend, C., Neal, A., Holmes, K., Lagendijk, A., Overman, J., D'Angelo, D., Omini, A., Hermkens, D., Lesieur, E., Liu, K., Ratnayaka, I., Corada, M., Bou-Gharios, G., Carroll, J., Dejana, E., Schulte-Merker, S., Hogan, B., Beltrame, M., De Val, S., Francois, M.
Development (Cambridge, England)   144(14): 2629-2639 (Journal)
Registered Authors
Beltrame, Monica, De Val, Sarah, Fritzsche, Martin, Hogan, Ben M., Neal, Alice, Schulte-Merker, Stefan
Arterial enhancer, Artery, Endothelial cell, Notch1, SoxF, Transcriptional regulation
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Arteries/embryology*
  • Arteries/metabolism*
  • Arteriovenous Malformations/embryology
  • Arteriovenous Malformations/genetics
  • Arteriovenous Malformations/metabolism
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Pregnancy
  • Receptor, Notch1/deficiency
  • Receptor, Notch1/genetics*
  • Receptor, Notch1/metabolism*
  • SOXF Transcription Factors/deficiency
  • SOXF Transcription Factors/genetics*
  • SOXF Transcription Factors/metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Zebrafish
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
28619820 Full text @ Development
Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the human NOTCH1 and zebrafish notch1b genes. These enhancers were able to direct arterial endothelial cell-restricted expression in transgenic models. Genetic disruption of SoxF binding sites established a clear requirement for members of this group of transcription factors (SOX7, SOX17 and SOX18) to drive the activity of these enhancers in vivo Endogenous deletion of the notch1b enhancer led to a significant loss of arterial connections to the dorsal aorta in Notch pathway-deficient zebrafish. Loss of SoxF function revealed that these factors are necessary for NOTCH1 and notch1b enhancer activity and for correct endogenous transcription of these genes. These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates.
Errata / Notes
This article is corrected by ZDB-PUB-220906-85 .
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes