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SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development
Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Clin Med, Oxford OX3 7DQ, England..
Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
Univ Oxford, Ludwig Inst Canc Res, Nuffield Dept Clin Med, Oxford OX3 7DQ, England..
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2017 (English)In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 144, no 14, 2629-2639 p.Article in journal (Refereed) Published
Abstract [en]

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 enhancerswere 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.

Place, publisher, year, edition, pages
COMPANY OF BIOLOGISTS LTD , 2017. Vol. 144, no 14, 2629-2639 p.
Keyword [en]
Notch1, SoxF, Artery, Arterial enhancer, Endothelial cell, Transcriptional regulation, Zebrafish, Human, Mouse
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:uu:diva-331237DOI: 10.1242/dev.146241ISI: 000405701000010PubMedID: 28619820OAI: oai:DiVA.org:uu-331237DiVA: diva2:1149467
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2017-10-16Bibliographically approved

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Dejana, Elisabetta

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