SOX18 directly interacts with MEF2C in endothelial cells

Recently, we demonstrated that mutations in the Sry-related HMG box gene So x18 underlie vascular and hair follicle defects in the mouse allelic mutant s ragged (Ra) and RaJ. Ra mice display numerous anomalies in the homozygote including, oedema, peritoneal secretions, and are almost completely naked. Sox18 and the MADS box transcription factor, Mef2C, are expressed in devel oping endothelial cells. Null mutants in Sox18 and Mef2c display overlappin g phenotypic abnormalities, hence, we investigated the relationship between these two DNA binding proteins. We report here the direct interaction betw een MEF2C and SOX18 proteins, and establish that these proteins are coexpre ssed in vivo in endothelial cell nuclei. MEF2C expression potentiates SOX18 -mediated transcription in vivo and regulates the function of the SOX18 act ivation domain. Interestingly, MEF2C fails to interact or co-activate trans cription with the Ra or RaJ mutant SOX18 proteins. These results suggest th at MEF2C and SOX18 may be important partners directing the transcriptional regulation of vascular development. (C) 2001 Academic Press.