The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27.

Abstract

We have cloned the human gene encoding the transcription factor T. T protein is vital for the formation of posterior mesoderm and axial development in all vertebrates. Brachyury mutant mice, which lack T protein, die in utero with abnormal notochord, posterior somites, and allantois. We have identified human T genomic clones and derived the mRNA sequence and gene structure. There is 91% amino acid identity between human and mouse T proteins overall and complete identity across 77 amino acids of the T-box motif within the DNA-binding domain. Human T expression is very similar to that found for T in other vertebrate species and is confined to cells derived from the notochord. The human T gene maps to chromosome 6q27 and is only the second human member of the T-box gene family to be described.

Dynamic Heterogeneity of Brachyury in Mouse Epiblast Stem Cells Mediates Distinct Response to Extrinsic Bone Morphogenetic Protein (BMP) Signaling

“…As embryonic development proceeds, T expression is restricted in the primitive streak during gastrulation from E6.5 to E7.5 ( Fig. 1) (48,53,54). Interestingly, the co-localization of T and pluripotent marker Oct4 in mouse embryos in vivo (Fig.…”

The Human T-Box Mesodermal Transcription Factor Brachyury Is a Candidate Target for T-Cell–Mediated Cancer Immunotherapy

“…The Brachyury gene was initially cloned from mouse developmental mutants characterized by an arrest in mesoderm formation (11) and was recognized as a relevant gene for the development of mesoderm during gastrulation. In fact, Brachyury is the founding member of a family of transcription factors, designated T-box transcription factors, characterized by a conserved DNA-binding domain (9), that has an essential role in the formation and organization of mesoderm in vertebrates (8,11,24,25). For example, in Xenopus, Brachyury is an early-immediate response gene of mesoderm inducers, such as activin or transforming growth factor-h, and injection In-labeled H441tumor cells were incubated with 25 Ag/mL of a control IgG, anti^HLA class I, or anti^HLA class II MAb for 1h before the addition of T-p2 Tcells.…”

“…Among a list of various genes highly represented in tumorderived libraries and rarely observed in normal tissue-derived libraries was the Unigene cluster Hs.389457, which contains the complete mRNA sequence of human Brachyury, a homologue of the mouse Brachyury gene (8). The product of the Brachyury gene is a member of the T-box family of transcription factors, characterized by a highly conserved DNA-binding domain designated as T-domain (9).…”

The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells

“…We previously demonstrated that the T-box transcription factor Brachyury (22)(23)(24) is highly expressed in various human tumors of epithelial origin and in human tumor cell lines derived from lung, colon, and prostate carcinomas, but not in most human normal adult tissues (25). We also demonstrated the potential of Brachyury as a target for T cell-mediated immunotherapy of cancer by identifying a CD8 + T cell epitope of Brachyury that was able to expand Brachyury-specific T cells from the blood of cancer patients with the ability to lyse Brachyury-positive tumor cell lines.…”