High impact information on zen

• Molecularly, retn seems to regulate sexual behavior via a previously described complex that represses zerknullt [1].
• Here we show that dl is a DNA-binding protein that specifically interacts with distal sequences of the zerknüllt (zen) promoter, one of the genetic targets of the morphogen [2].
• These zen sequences have the properties of a silencer element and can act over long distances to repress the expression of a heterologous promoter [2].
• It is interesting that cotransfection with combinations of expression vectors encoding the homeobox proteins fushi tarazu, paired, and/or zen resulted in substantial synergistic increases in expression [3].
• This effect requires a sequence termed a negative regulatory element (NRE), found adjacent to Dorsal-binding sites in the zen promoter and adjacent to the NF-kappa B-binding site in the human interferon-beta (IFN-beta) enhancer [4].

Biological context of zen

• A chromosome walk initiated to reach the proboscipedia gene of D. subobscura reveals that the distance between pb and zen is at least four times the one described for D. melanogaster and for D. pseudoobscura [5].
• We also describe a transcription unit very close to pb, which is expressed dorsally during embryogenesis in a pattern resembling that of the nearby zygotic lethal zerknüllt (zen) locus [6].
• The occurrence of closely linked homeo box genes that display similar patterns of expression is not unique to the zen locus [7].
• We found that T-rich sequences close to the dl binding sites in the silencer region of the zen promoter are conserved between three Drosophila species [8].
• We discuss a comparison of the DNA sequences from the zen and tld promoters and the possible mechanisms of transcriptional silencing [9].

Anatomical context of zen

• We have used P-element-mediated germ line transformation to show that z1 alone can provide zen+ gene function, suggesting that the z2 gene might be dispensable [7].
• Here we analyze the regulation of the Drosophila gene zen, which is a target of the Decapentaplegic (Dpp) signaling pathway during cellular blastoderm formation [10].
• Subsequent interactions with other zygotic D/V regulatory genes refine the zen pattern, restricting expression to the dorsal-most ectoderm [11].
• Previous studies have shown that dl activates the mesoderm determinant twist (twi); here we use a combination of site-directed mutagenesis and P-transformation assays to demonstrate that it also functions as a direct transcriptional repressor of a second target gene, zerknüllt (zen) [12].
• We also show that in HeLa cells, as assayed by transient transfection, expression of DSP1 increases activation by Dorsal from the twist promoter and inhibits that activation from the zen promoter, consistent with the previously proposed idea that DSP1 can affect the action of Dorsal in a promoter-specific fashion [13].

Regulatory relationships of zen

• Here we show Zen downregulates DREF gene promoter activity through action on the region between +241 and +254 (5'-AGAATACTCAACA) [14].
• In addition, we demonstrate that ectopically expressed Zen can activate targets like Race in the presence of low level Smads, indicating that the role of the highest activity of the BMP gradient is to activate zen [15].

Other interactions of zen

• Molecular characterization of the zerknüllt region of the Antennapedia complex of D. subobscura [5].
• The putative proteins encoded by z1 and z2 are highly divergent and are related only by virtue of homeo box homology [7].
• Transcriptional regulation of the Drosophila gene zen by competing Smad and Brinker inputs [10].
• However, a protein consisting only of the Rel homologous region still acts as a weak repressor of zerknüllt transcription [16].
• Combinatorial expression of a ftz-zen fusion promoter suggests the occurrence of cis interactions between genes of the ANT-C [17].

Analytical, diagnostic and therapeutic context of zen

• PCR reactions were performed with degenerate oligonucleotide primers coding for the highly conserved regions of the homeodomains of the Drosophila Antennapedia, bicoid, and zerknüllt proteins [18].

References