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dc.contributor.authorLilly, Andrew J
dc.contributor.authorCosta, Guilherme
dc.contributor.authorLargeot, Anne
dc.contributor.authorFadlullah, Muhammad Z H
dc.contributor.authorLie-A-Ling, Michael
dc.contributor.authorLacaud, Georges
dc.contributor.authorKouskoff, Valerie
dc.date.accessioned2016-11-18T12:46:09Z
dc.date.available2016-11-18T12:46:09Z
dc.date.issued2016-10-17
dc.identifier.citationInterplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac. 2016 Developmenten
dc.identifier.issn1477-9129
dc.identifier.pmid27802172
dc.identifier.doi10.1242/dev.140970
dc.identifier.urihttp://hdl.handle.net/10541/620023
dc.description.abstractEndothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Whilst the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, whilst having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity. Through this interaction we demonstrate that SOX7 hinders RUNX1 DNA binding as well as the interaction between RUNX1 and its cofactor CBFβ. Finally, we show by single cell expression profiling and immunofluorescence that SOX7 is broadly expressed across the RUNX1(+) yolk sac HE population compared with SOX17. Collectively, these data demonstrate for the first time how direct protein-protein interactions between endothelial and hematopoietic transcription factors regulate contrasting transcriptional programs during HE differentiation and EHT.
dc.languageENG
dc.language.isoenen
dc.rightsArchived with thanks to Development (Cambridge, England)en
dc.titleInterplay between SOX7 and RUNX1 regulates hemogenic endothelial fate in the yolk sac.en
dc.typeArticleen
dc.contributor.departmentStem Cell Hematopoiesis, Cancer Research UK Manchester Institute, The University of Manchester, Wilmslow road, M20 4BXen
dc.identifier.journalDevelopmenten
refterms.dateFOA2020-04-21T07:46:32Z
html.description.abstractEndothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Whilst the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, whilst having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity. Through this interaction we demonstrate that SOX7 hinders RUNX1 DNA binding as well as the interaction between RUNX1 and its cofactor CBFβ. Finally, we show by single cell expression profiling and immunofluorescence that SOX7 is broadly expressed across the RUNX1(+) yolk sac HE population compared with SOX17. Collectively, these data demonstrate for the first time how direct protein-protein interactions between endothelial and hematopoietic transcription factors regulate contrasting transcriptional programs during HE differentiation and EHT.


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