Kispert A, Herrmann B G
Max-Planck-Institut für Entwicklungsbiologie, Abt. Biochemie, Tübingen, Germany.
EMBO J. 1993 Aug;12(8):3211-20. doi: 10.1002/j.1460-2075.1993.tb05990.x.
Brachyury (T) mutant embryos are deficient in mesoderm formation and do not complete axial development. The notochord is most strongly affected. The T gene is expressed transiently in primitive streak-derived nascent and migrating mesoderm cells and continuously in the notochord. Ectopic expression of T protein in the animal cap of Xenopus embryos results in ectopic mesoderm formation. The T protein is located in the nucleus. These and other data suggested that the T gene might be involved in the control of transcriptional regulation. In an attempt to demonstrate specific DNA binding of the T protein we have identified a consensus sequence among DNA fragments selected from a mixture of random oligomers. Under our experimental conditions T protein binds as a monomer to DNA. This property resides in the N-terminal domain of 229 amino acid residues which is strongly conserved between the mouse protein, and its Xenopus and zebrafish homologues. The latter proteins also recognize the consensus DNA binding site. We suggest that the T protein is involved in the control of genes required for mesoderm formation, and for the differentiation and function of chorda mesoderm.
短尾(T)突变胚胎在中胚层形成方面存在缺陷,无法完成轴向发育。脊索受影响最为严重。T基因在原条衍生的新生和迁移中胚层细胞中短暂表达,并在脊索中持续表达。在非洲爪蟾胚胎的动物帽中异位表达T蛋白会导致异位中胚层形成。T蛋白位于细胞核中。这些以及其他数据表明,T基因可能参与转录调控的控制。为了证明T蛋白与DNA的特异性结合,我们在从随机寡聚物混合物中选择的DNA片段中鉴定出了一个共有序列。在我们的实验条件下,T蛋白以单体形式与DNA结合。这种特性存在于由229个氨基酸残基组成的N端结构域中,该结构域在小鼠蛋白及其非洲爪蟾和斑马鱼同源物之间高度保守。后两种蛋白也能识别共有DNA结合位点。我们认为,T蛋白参与了中胚层形成以及脊索中胚层分化和功能所需基因的控制。