Hosking B M, Wang S C, Chen S L, Penning S, Koopman P, Muscat G E
Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Queensland, Australia.
Biochem Biophys Res Commun. 2001 Sep 21;287(2):493-500. doi: 10.1006/bbrc.2001.5589.
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.
最近，我们证明了与性别决定基因SRY相关的高迁移率族盒基因Sox18的突变是小鼠等位基因突变体ragged（Ra）和RaJ中血管和毛囊缺陷的基础。Ra小鼠在纯合子中表现出许多异常，包括水肿、腹腔分泌物，并且几乎完全无毛。Sox18和MADS盒转录因子Mef2C在发育中的内皮细胞中表达。Sox18和Mef2c的基因敲除突变体表现出重叠的表型异常，因此，我们研究了这两种DNA结合蛋白之间的关系。我们在此报告MEF2C和SOX18蛋白之间的直接相互作用，并证实这些蛋白在体内内皮细胞核中共表达。MEF2C的表达在体内增强了SOX18介导的转录，并调节SOX18激活域的功能。有趣的是，MEF2C无法与Ra或RaJ突变体SOX18蛋白相互作用或共同激活转录。这些结果表明，MEF2C和SOX18可能是指导血管发育转录调控的重要伙伴。
