SOX18 directly interacts with MEF2C in endothelial cells.
Recently, we demonstrated that mutations in the Sry-related HMG box gene Sox18 underlie vascular and hair follicle defects in the mouse allelic mutants 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 developing endothelial cells. Null mutants in Sox18 and Mef2c display overlapping phenotypic abnormalities, hence, we investigated the relationship between these two DNA binding proteins. We report here the direct interaction between MEF2C and SOX18 proteins, and establish that these proteins are coexpressed in vivo in endothelial cell nuclei. MEF2C expression potentiates SOX18-mediated transcription in vivo and regulates the function of the SOX18 activation domain. Interestingly, MEF2C fails to interact or co-activate transcription with the Ra or RaJ mutant SOX18 proteins. These results suggest that MEF2C and SOX18 may be important partners directing the transcriptional regulation of vascular development.
Hosking
B M
BM
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Queensland, Australia.
Wang
S C
SC
Chen
S L
SL
Penning
S
S
Koopman
P
P
Muscat
G E
GE
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D051379:Mice; D009154:Mutation; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D055760:SOXF Transcription Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D006609:High Mobility Group Proteins; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; C490653:Sox18 protein, mouse; D014157:Transcription Factors