Kusch T et al. (2002), Brachyury proteins regulate target genes throug...

XB-ART-7625

Genes Dev 2002 Feb 15;164:518-29. doi: 10.1101/gad.213002.

Show Gene links Show Anatomy links

Brachyury proteins regulate target genes through modular binding sites in a cooperative fashion.

Kusch T , Storck T , Walldorf U , Reuter R .

???displayArticle.abstract???
Brachyury proteins, a conserved subgroup of the T domain transcription factors, specify gut and posterior mesoderm derivatives throughout the animal kingdom. The T domain confers DNA-binding properties to Brachyury proteins, but little is known how these proteins regulate their target genes. We characterized a direct target gene of the Drosophila Brachyury-homolog Brachyenteron. Brachyenteron activates the homeobox gene orthopedia in a dose-dependent manner via multiple binding sites with the consensus (A/G)(A/T)(A/T)NTN(A/G)CAC(C/T)T. The sites and their A/T-rich flanking regions are conserved between D. melanogaster and Drosophila virilis. Reporter assays and site-directed mutagenesis demonstrate that Brachyenteron binding sites confer in part additive, in part synergistic effects on otp transcription levels. This suggests an interaction of Brachyenteron proteins on the DNA, which we could map to a conserved motif within the T domain. Mouse Brachyury also interacts with Brachyenteron through this motif. We further show that the Xenopus and mouse Brachyury homologs activate orthopedia expression when expressed in Drosophila embryonic cells. We propose that the mechanisms to achieve target gene expression through variable binding sites and through defined protein-protein interactions might be conserved for Brachyury relatives.

???displayArticle.pubmedLink??? 11850413
???displayArticle.pmcLink??? PMC155342
???displayArticle.link??? Genes Dev

Species referenced: Xenopus laevis
Genes referenced: otp tbxt

References [+] :

Bachmann, Positive and negative control of Serrate expression during early development of the Drosophila wing. 1998, Pubmed

Bachmann, Positive and negative control of Serrate expression during early development of the Drosophila wing. 1998, Pubmed
Bassham, Brachyury (T) expression in embryos of a larvacean urochordate, Oikopleura dioica, and the ancestral role of T. 2000, Pubmed
Brand, Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. 1993, Pubmed
Burz, Cooperative DNA-binding by Bicoid provides a mechanism for threshold-dependent gene activation in the Drosophila embryo. 1998, Pubmed
Carreira, Brachyury-related transcription factor Tbx2 and repression of the melanocyte-specific TRP-1 promoter. 1998, Pubmed
Casey, The T-box transcription factor Brachyury regulates expression of eFGF through binding to a non-palindromic response element. 1998, Pubmed , Xenbase
Driever, The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. 1989, Pubmed
Häder, Receptor tyrosine kinase signaling regulates different modes of Groucho-dependent control of Dorsal. 2000, Pubmed
Hinz, The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes. 1994, Pubmed
Hiromi, Regulation and function of the Drosophila segmentation gene fushi tarazu. 1987, Pubmed
Hurlin, Mga, a dual-specificity transcription factor that interacts with Max and contains a T-domain DNA-binding motif. 1999, Pubmed
Isaac, Tbx genes and limb identity in chick embryo development. 1998, Pubmed
James, Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. 1996, Pubmed
Kispert, The T protein encoded by Brachyury is a tissue-specific transcription factor. 1995, Pubmed
Kispert, The Brachyury gene encodes a novel DNA binding protein. 1993, Pubmed , Xenbase
Kispert, Homologs of the mouse Brachyury gene are involved in the specification of posterior terminal structures in Drosophila, Tribolium, and Locusta. 1994, Pubmed
Krasnow, Transcriptional activation and repression by Ultrabithorax proteins in cultured Drosophila cells. 1989, Pubmed
Kusch, Functions for Drosophila brachyenteron and forkhead in mesoderm specification and cell signalling. 1999, Pubmed , Xenbase
Lamolet, A pituitary cell-restricted T box factor, Tpit, activates POMC transcription in cooperation with Pitx homeoproteins. 2001, Pubmed
MacMurray, The antimorphic nature of the Tc allele at the mouse T locus. 1988, Pubmed
Müller, Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor. 1997, Pubmed , Xenbase
O'Reilly, Patterning of the mesoderm in Xenopus: dose-dependent and synergistic effects of Brachyury and Pintallavis. 1995, Pubmed , Xenbase
Peterson, A comparative molecular approach to mesodermal patterning in basal deuterostomes: the expression pattern of Brachyury in the enteropneust hemichordate Ptychodera flava. 1999, Pubmed
Rodriguez-Esteban, The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity. 1999, Pubmed
Shoguchi, A starfish homolog of mouse T-brain-1 is expressed in the archenteron of Asterina pectinifera embryos: possible involvement of two T-box genes in starfish gastrulation. 2000, Pubmed , Xenbase
Simeone, Orthopedia, a novel homeobox-containing gene expressed in the developing CNS of both mouse and Drosophila. 1994, Pubmed
Singer, Drosophila brachyenteron regulates gene activity and morphogenesis in the gut. 1996, Pubmed
Smith, T-box genes: what they do and how they do it. 1999, Pubmed
Stott, Rescue of the tail defect of Brachyury mice. 1993, Pubmed
Tada, Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm. 1998, Pubmed , Xenbase
Technau, HyBra1, a Brachyury homologue, acts during head formation in Hydra. 1999, Pubmed
Wattler, A combined analysis of genomic and primary protein structure defines the phylogenetic relationship of new members if the T-box family. 1998, Pubmed
Woollard, The caenorhabditis elegans fate-determining gene mab-9 encodes a T-box protein required to pattern the posterior hindgut. 2000, Pubmed