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Homodimerization regulates an endothelial specific signature of the SOX18 transcription factor.

ABSTRACT: During embryogenesis, vascular development relies on a handful of transcription factors that instruct cell fate in a distinct sub-population of the endothelium (1). The SOXF proteins that comprise SOX7, 17 and 18, are molecular switches modulating arterio-venous and lymphatic endothelial differentiation (2,3). Here, we show that, in the SOX-F family, only SOX18 has the ability to switch between a monomeric and a dimeric form. We characterized the SOX18 dimer in binding assays in vitro, and using a split-GFP reporter assay in a zebrafish model system in vivo. We show that SOX18 dimerization is driven by a novel motif located in the vicinity of the C-terminus of the DNA binding region. Insertion of this motif in a SOX7 monomer forced its assembly into a dimer. Genome-wide analysis of SOX18 binding locations on the chromatin revealed enrichment for a SOX dimer binding motif, correlating with genes with a strong endothelial signature. Using a SOX18 small molecule inhibitor that disrupts dimerization, we revealed that dimerization is important for transcription. Overall, we show that dimerization is a specific feature of SOX18 that enables the recruitment of key endothelial transcription factors, and refines the selectivity of the binding to discrete genomic locations assigned to endothelial specific genes.

SUBMITTER: Moustaqil M

PROVIDER: S-EPMC6265484 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Homodimerization regulates an endothelial specific signature of the SOX18 transcription factor.

Moustaqil Mehdi M Fontaine Frank F Overman Jeroen J McCann Alex A Bailey Timothy L TL Rudolffi Soto Paulina P Bhumkar Akshay A Giles Nichole N Hunter Dominic J B DJB Gambin Yann Y Francois Mathias M Sierecki Emma E

Nucleic acids research 20181101 21

During embryogenesis, vascular development relies on a handful of transcription factors that instruct cell fate in a distinct sub-population of the endothelium (1). The SOXF proteins that comprise SOX7, 17 and 18, are molecular switches modulating arterio-venous and lymphatic endothelial differentiation (2,3). Here, we show that, in the SOX-F family, only SOX18 has the ability to switch between a monomeric and a dimeric form. We characterized the SOX18 dimer in binding assays in vitro, and using ...[more]

PMID: 30335167

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Homodimerization regulates an endothelial specific signature of the SOX18 transcription factor.

Publications

Homodimerization regulates an endothelial specific signature of the SOX18 transcription factor.

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