Disease relevance of ftz

• The embryonic ftz protein migrates more slowly on SDS-polyacrylamide gels than protein made either in E. coli or in a reticulocyte lysate system in vitro, indicating that it is modified in the embryo [1].
• To demonstrate this, we targeted the promoter of the well-characterized fushi tarazu (ftz) gene with a ZFP TF activator using the VP16 activation domain from Herpes simplex virus, and ZFP TF repressors using the Drosophila methyl-CpG binding domain (MBD)-like Delta protein [2].
• If the ftz gene is prevented from functioning, alternating portions of the body normally derived from the active stripes fail to develop, resulting in larvae which lack the denticle bands normally formed by the mesothorax and odd-numbered abdominal segments (that is, thoracic segment T2 and abdominal segments A1, A3, A5 and A7) [3].

High impact information on ftz

• Naked, microinjected fushi tarazu (ftz) transcripts do not localize in blastoderm embryos, indicating that cytoplasmic mechanisms alone are insufficient for apical targeting [4].
• Certain genes, such as ftz, are largely negatively regulated in the interstripes through proximal upstream elements by the striped expression of other pair-rule genes, while others, such as hairy and eve, are largely regulated through distal upstream elements by the aperiodic gap genes (Figure 7) [5].
• Fushi tarazu and engrailed are two of the genes required for proper segmentation of the Drosophila embryo [6].
• Using a cotransfection assay, we have shown that homeodomain proteins encoded by the homeotic gene Antennapedia (Antp) and the segmentation gene fushi tarazu, as well as a hybrid homeodomain protein, are activators of transcription from specific promoters in cultured Drosophila cells [7].
• The altered specificity Bicoid mutants recognized DNA sites bound by Ultrabithorax, fushi tarazu, and other related homeo-domain proteins [8].

Chemical compound and disease context of ftz

• Since embryonic ftz protein migrates more slowly on SDS polyacrylamide gels than protein expressed either in E. coli, or in vitro in a reticulocyte lysate system, it is apparently modified in the embryo [9].
• Activation domains derived from herpes simplex viral protein VP16, the Drosophila fushi tarazu glutamine-rich domain (ftzQ), and yeast Gal4 were tested in transient assays [10].

Biological context of ftz

• We report a systematic mutational analysis of the helix-turn-helix motif (HTH) of the fushi tarazu (ftz) homeo domain (HD) of Drosophila [11].
• Direct activation of homeotic gene control regions by ftz (or eve) protein may be a regulatory step which is generally used to align expression of homeotic genes with parasegmental boundaries [12].
• Using a heat-shock-inducible run transgene, we found that ectopic run expression leads to rapid repression of eve stripes and a somewhat delayed expansion of ftz stripes [13].
• We show that fusion gene expression is transcriptionally regulated, such that ectopic expression is suppressed when pattern is established, and present evidence indicating that interstripe hb-ftz expression is repressed by eve [14].
• Examination of the phenotype of ftz Rg-pbx- double-mutant embryos did not reveal a clear pattern of epistasis between the genes nor was absolute additivity of phenotype seen [15].

Anatomical context of ftz

• Regulation of segment polarity genes in the Drosophila blastoderm by fushi tarazu and even skipped [16].
• In addition, en and twi products activate the enhancer, probably directly. en broadens the parasegmental stripe while twi cooperates with ftz to enhance expression in the mesoderm [17].
• In contrast, the Fushi Tarazu homeodomain protein is an activator, both in cultured cells and in Drosophila embryos, where it activates several known target genes, including its own gene [18].
• The Fushi tarazu homeodomain also causes neurite outgrowth in UR61 cells and the neurotrophic activities of Engrailed and Fushi tarazu homeodomains correlate with their DNA binding specificities [19].
• In the absence of ftz CNS expression, some neurons appear normal (for example, the aCC, pCC, and RP1), whereas the RP2 neuron extends its growth cone along an abnormal pathway, mimicking its sibling (RP1), suggesting a transformation in neuronal identity [20].

Associations of ftz with chemical compounds

• These effects appear to result from stabilization of the ftz protein, since ftz stripes decay much more slowly in mutant embryos than in wild type after injection of the protein synthesis inhibitor cycloheximide [21].
• The mobility shift assay was used to study the competition of the minor groove binder distamycin A with either an Antennapedia homeodomain (Antp HD) peptide or derivatives of a fushi tarazu homeodomain (ftz HD) peptide for their AT-rich DNA binding site [22].
• FTZ-F1, a steroid hormone receptor-like protein implicated in the activation of fushi tarazu [23].
• This interaction required the AF-2 core and putative ligand-binding domain of FTZ-F1 and the LXXLL motif of FTZ [24].
• Here we show that the activity of the glutamine-rich fushi tarazu activation domain is indeed blocked by truncated TFIIB derivatives in Drosophila Schneider L2 cells, suggesting that it is mediated by interactions with TFIIB [25].

Physical interactions of ftz

• Restriction fragments containing ftz homeodomain binding sites were identified within a 90 kb stretch of DNA extending the Antp P1 and P2 promoters [26].
• The tramtrack gene encodes a Drosophila finger protein that interacts with the ftz transcriptional regulatory region and shows a novel embryonic expression pattern [27].
• The Drosophila nuclear receptors FTZ-F1 alpha and FTZ-F1 beta compete as monomers for binding to a site in the fushi tarazu gene [28].
• The correct activation of Antennapedia and bithorax complex genes requires the fushi tarazu gene [29].
• Our results strongly suggest that Hairy normally acts as a promoter-bound repressor of fushi tarazu, runt and odd-skipped, and that Runt directly represses even-skipped [30].

Regulatory relationships of ftz

• Here we present evidence that the 69-kDa ttk protein can indeed repress expression not only of ftz, but also of eve [31].
• Ftz/Ftz-F1 activate Sulf1 expression in blastoderm embryos via composite binding sites [32].
• Fusion of ftz to the Tubalpha1 promoter resulted in low-level ectopic expression of FTZ relative to FTZ expressed from the endogenous ftz gene [33].
• How does the fushi tarazu gene activate engrailed in the Drosophila embryo [34]?
• Chromatin remodeling mediated by Drosophila GAGA factor and ISWI activates fushi tarazu gene transcription in vitro [35].

Other interactions of ftz

• We propose that the anterior margin of each ftz stripe is normally defined by the posterior even-skipped (eve) boundary [36].
• We have observed that the transcription of several genes, including ftz, is triggered in embryos at a critical nuclear density; therefore, we suggest that titration of transcription factors like ttk by the nucleocytoplasmic ratio triggers zygotic transcription in Drosophila [37].
• Footprint analysis and tests in transformed embryos of constructs bearing mutated footprint regions suggest that ftz protein acts directly as a transcriptional activator of Ubx [12].
• DNA from each of these 3' exons also hybridized weakly to DNA from the fushi tarazu locus of the ANT-C [38].
• By contrast, the specific combination of Runt + Ftz is sufficient for slp1 repression in all blastoderm nuclei [39].

Analytical, diagnostic and therapeutic context of ftz

• The structure of the ftz gene has been analyzed by S1 nuclease mapping and by restriction mapping of a cDNA clone [40].
• Analysis of embryonic ftz protein on Western blots permitted us to approximate the number of protein molecules per nucleus [1].
• We have examined the expression pattern of the segmentation gene fushi tarazu (ftz) by in situ hybridization to whole mount embryos using digoxygenin labeled probes [41].
• Sequence determination of these regions reveals that both human DNA sequences contain a region capable of coding 61 amino acids, which shares greater than 90% homology with the peptide sequences specified by the homeo box domain of Drosophila homeotic genes, Antennapedia, fushi tarazu, and Ultrabithorax [42].
• Their protein products Fushi tarazu and Engrailed (Ftz and En) each contain a homeodomain and have been shown to act as transcriptional regulators in transient expression experiments in a Drosophila cell culture system [6].

References