THE BRACHYURY GENE ENCODES A NOVEL DNA-BINDING PROTEIN

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.