Disease relevance of eve

• In the most thoroughly characterized combination (odd eve), both naked cuticle and specific denticle rows are restored that would normally have been deleted by one of the two mutants alone [1].
• It corrects the defect in Chinese hamster ovary (CHO) mutants of NER complementation group 4 and is implicated in complementation group F of the human disorder xeroderma pigmentosum [2].

High impact information on eve

• Drosophila Atrophin directly binds to Even-skipped in vitro [3].
• Two D-STAT-binding sites were identified within the eve stripe 3 enhancer region [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].
• We also show that eve represses expression from the Ubx promoter in Drosophila tissue culture cells, again in a binding site-dependent manner [6].
• Deletion of eve DNA binding sites does not alter transcription in the absence of eve, and so repression is not likely to be the result of eve competitively inhibiting an activator protein from binding to the same DNA element [6].

Biological context of eve

• 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 [7].
• In an effort to determine how crude gradients of transcriptional activators and repressors specify sharp stripes of gene expression in the early embryo, we have conducted a detailed study of even-skipped (eve) stripe 2 [8].
• The eve stripe 2 enhancer employs multiple modes of transcriptional synergy [9].
• To better understand its mechanism of action, we functionally dissected the Even-skipped protein in the context of this transgene [10].
• Finally, homologues of Eve from diverse species were able to rescue the eve mutant phenotype, indicating conservation of both targeting and repression functions in the nervous system [11].

Anatomical context of eve

• Here, we study the mechanisms by which positional information conveyed by signaling pathways and a combinatorial code of activating and repressing transcription factors work together to confine the expression of the homeobox gene even-skipped (eve) to a small region of the dorsal mesoderm [12].
• A chimeric protein consisting only of the Engrailed repressor domain and the Even-skipped homeodomain, but not the homeodomain alone, was able to restore function, indicating that the repression of target genes is sufficient for even skipped function at the blastoderm stage, while the homeodomain is sufficient to recognize those target genes [10].
• Consistent with this, expression of Even-skipped (Eve) protein in heart precursor and muscle cells, which is dependent on Wg signaling in Drosophila, is also conserved in mysids [13].
• A second expression pattern emerges during neurogenesis, whereby eve protein is detected in discrete subsets of neurons in each of the ventral ganglia [14].
• We found that even-skipped (eve) function is crucially required for homeotic gene expression, whereas most other segmentation mutations have only minor effects on position and/or width of the homeotic expression domains in this germ layer [15].

Associations of eve with chemical compounds

• Our results also show that repression by TTK69 of GAGA-dependent activation of the eve promoter is not mediated by any of the co-repressors known to interact with TTK69 (dMi2 or C-terminal binding protein) or by trichostatin A-sensitive histone deacetylases [16].
• Comparison of chicken aldehyde reductase with mammalian aldehyde reductases gave values in the range 6.8 - 9.9 suggesting a close relationship whereas the difference indexes for the enzymes from fruit fly and Baker's yeast versus vertebrate aldehyde reductases (10.9 - 14.4) indicate more distant relationships [17].
• A 10.5 kb genomic fragment that spans the P insertion sites has been found to restore methyl methanesulfonate resistance and female fertility of the mei-41D3 mutants [18].

Physical interactions of eve

• Together, these data show that the eve enhancer integrates several regulatory pathways via the combinatorial binding of the mesoderm-intrinsic regulator Tin and the effectors of the Dpp and Wg signals [19].
• As with many Drosophila genes, eve contains at its promoter region binding sites for GAGA and TTK [20].
• Binding of eve protein is shown to exclude binding by zeste protein [21].

Regulatory relationships of eve

• Meanwhile targeted ectopic Dll represses eve expression and hindgut formation [22].
• Antibody studies confirm that expression of eve is suppressed by duplications of esc [23].
• The pair-rule segmentation gene even skipped (eve) is required to activate engrailed stripes and to organize odd-numbered parasegments (PSs) [24].
• Drosophila homeobox gene eve enhances trol, an activator of neuroblast proliferation in the larval CNS [25].
• We propose that a combination of segmentation gene products that activates the expression of eve represses the expression of ftz, and vice versa [26].

Other interactions of eve

• We propose that the anterior margin of each ftz stripe is normally defined by the posterior even-skipped (eve) boundary [27].
• We demonstrate further that a mesodermally active enhancer of eve contains several Smad and Tin binding sites that are essential for enhancer activity in vivo [19].
• The lack of Dll function in the anal primordia transforms the anal tissue into hindgut by the extension of the eve domain [22].
• Surprisingly, flies carrying duplications of extra sex combs (esc), that were heterozygous for mutations of even-skipped (eve), were extremely subvital [23].
• Duplications of nine other Pc group genes have no detectable effect on eve [23].

Analytical, diagnostic and therapeutic context of eve

• Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRalpha-96Aa [28].
• Although ryk RNA is expressed at similar levels in a variety of tissues from embryonic day 10.5 to 18.5, specific induction of ryk RNA can be seen by in situ hybridization in the basal layer of skin and hair follicle at day 15.5-16.5, and protein staining localizes to the hair follicle by immunohistochemistry [29].
• Results of in situ hybridization to whole embryos and immunohistochemical analyses indicated that EHD1 expression was already noted at day 9.5 in the limb buds and pharyngeal arches and at day 10.5 in sclerotomes, at various elements of the branchial apparatus (mandible and hyoid), and in the occipital region [30].
• We report the purification, crystallization, and preliminary diffraction analysis of the Drosophila Even-skipped homeodomain (Eve HD) bound to two different oligonucleotides [31].

References