The Brachyury gene encodes a novel DNA binding protein

Area of Science:

• Developmental Biology
• Molecular Genetics
• Transcriptional Regulation

Background:

• Brachyury (T) mutant embryos exhibit defects in mesoderm formation and axial development, with the notochord being significantly impacted.
• The T gene's expression pattern in primitive streak-derived mesoderm and notochord suggests a role in cell differentiation and patterning.

Purpose of the Study:

• To investigate the molecular mechanism underlying the Brachyury (T) gene's function in embryonic development.
• To determine if the T protein directly binds DNA and identify its DNA-binding domain.

Main Methods:

• Identification of a consensus DNA sequence recognized by the T protein using DNA selection assays.
• Analysis of T protein DNA-binding properties, including monomeric binding and domain localization.
• Comparative analysis of T protein homologues in Xenopus and zebrafish.

Main Results:

• The T protein binds as a monomer to a specific consensus DNA sequence.
• The DNA-binding activity is localized to the N-terminal domain of 229 amino acids.
• Conserved DNA-binding sites and recognition were observed in Xenopus and zebrafish T proteins.

Conclusions:

• The T protein functions as a transcriptional regulator, directly binding to DNA.
• This DNA-binding activity is essential for controlling genes involved in mesoderm formation and notochord differentiation.
• The conserved nature of the T protein's DNA-binding domain highlights its fundamental role across species.