Hoser Melanie, Potzner Michaela R, Koch Julia M C, Bösl Michael R, Wegner Michael, Sock Elisabeth
Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Erlangen, Germany.
Mol Cell Biol. 2008 Aug;28(15):4675-87. doi: 10.1128/MCB.00338-08. Epub 2008 May 27.
The transcription factors Sox4 and Sox11 are important regulators of diverse developmental processes including heart, lung, pancreas, spleen, and B-cell development. Here we have studied the role of the related Sox12 as the third protein of the SoxC group both in vivo and in vitro. Despite widespread Sox12 expression during embryonic development, Sox12-deficient mice developed surprisingly normally, so that they were born alive, showed no gross phenotypic abnormalities, and were fertile in both sexes. Comparison with the related Sox4 and Sox11 revealed extensive overlap in the embryonic expression pattern but more uniform expression levels for Sox12, without sites of particularly high expression. All three Sox proteins furthermore exhibited comparable DNA-binding characteristics and functioned as transcriptional activators. Sox12 was, however, a relatively weak transactivator in comparison to Sox11. We conclude that Sox4 and Sox11 function redundantly with Sox12 and can compensate its loss during mouse development. Because of differences in expression levels and transactivation rates, however, functional compensation is not reciprocal.
转录因子Sox4和Sox11是多种发育过程的重要调节因子,包括心脏、肺、胰腺、脾脏和B细胞发育。在此,我们研究了相关的Sox12作为SoxC组的第三种蛋白质在体内和体外的作用。尽管Sox12在胚胎发育过程中广泛表达,但Sox12基因缺失的小鼠发育却出奇地正常,它们能存活出生,没有明显的表型异常,并且两性均具有生育能力。与相关的Sox4和Sox11比较发现,它们在胚胎表达模式上有广泛重叠,但Sox12的表达水平更均匀,没有特别高表达的位点。此外,所有这三种Sox蛋白都表现出类似的DNA结合特性,并作为转录激活因子发挥作用。然而,与Sox11相比,Sox12是一个相对较弱的反式激活因子。我们得出结论,Sox4和Sox11与Sox12功能冗余,并且在小鼠发育过程中可以补偿其缺失。然而,由于表达水平和反式激活率的差异,功能补偿并非相互的。