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SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development.
- Source :
-
Development (Cambridge, England) [Development] 2017 Jul 15; Vol. 144 (14), pp. 2629-2639. Date of Electronic Publication: 2017 Jun 15. - Publication Year :
- 2017
-
Abstract
- 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.<br />Competing Interests: Competing interestsThe authors declare no competing or financial interests.<br /> (© 2017. Published by The Company of Biologists Ltd.)
- Subjects :
- Amino Acid Sequence
Animals
Animals, Genetically Modified
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
SOXF Transcription Factors deficiency
Sequence Homology, Amino Acid
Signal Transduction
Zebrafish
Zebrafish Proteins deficiency
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Arteries embryology
Arteries metabolism
Receptor, Notch1 genetics
Receptor, Notch1 metabolism
SOXF Transcription Factors genetics
SOXF Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9129
- Volume :
- 144
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 28619820
- Full Text :
- https://doi.org/10.1242/dev.146241