zeste

DEVELOPMENTAL BIOLOGY

The expression of the zeste gene varies through the life cycle of the fly. Its transcription is most abundant in maternal RNA, declines to very low levels during larval growth, but rises again in late third instar larvae and pupae. Nearly ubiquitous expression of zeste is found in late embryos and first instar larvae, but disappears almost completely except in brain and gonads by third instar larva. Shortly before pupation expression rises again in imaginal discs, Malpighian tubules, and salivary glands, and again becomes nearly ubiquitous in pupae. zeste continues to be expressed in adult brain and gonads. Wild-type salivary gland chromosomes contain about 60 strong bands of Zeste immunofluorescence at specific cytological locations. After heat induction of larvae containing the hs-zeste gene, many hundreds of bands appear. Such results suggest the involvement of zeste in the expression of a wide variety of genes at different developmental stages (Pirrotta, 1988).

Effects of Mutation or Deletion

The original zeste mutant (in both males and females) has a distinctly dilute eye color that grows brown with age. Transvection is the effect of regulatory elements of one copy of a target gene on the expression of a second copy of the gene on a homologously paired chromosome. Such transvection effects were first observed in the Ultrabithorax (Ubx) gene. The effect is dependent on zeste (Kaufman, 1972).

Mutations in zeste do dot affect the cis-regulation of endogenous Ubx, but expression of small Ubx promoter constructs are strongly dependent on zeste. This difference is due to redundant cis-regulatory elements in the Ubx gene, which presumably contain binding sites for factors that overlap in function with Zeste. (Laney, 1996).

Flies doubly heterozygous for GAGA (synonym: trithorax like) and Ubx exhibit larger halteres than flies mutant for Ubx alone, and, with incomplete penetrance and variable expressivity, show homeotic transformations of the haltere and postnotum into wing. When zeste mutations are crossed into this double heterozygotic background, a similar range of phenotypes is observed. However, the fraction of animals displaying the enhanced Ubx phenotype is increased 2 to 19 fold, depending on the GAGA allele used. This increase in penetrance is observed with two different zeste alleles. Therefore, mutations in zeste increase the likelihood that limiting amouts of GAGA factor and UBX will lead to reduced expression of Ubx and to homeotic transformation of haltere into wing (Laney, 1996).

The zeste1 (z1) mutation of the zeste gene produces a mutant yellow eye color instead of the wild-type red. Genetic and molecular data suggest that z1 achieves this change by altering expression of the wild-type white gene in a manner that exhibits transvection effects. There exist suppressor and enhancer mutations that modify the z1 eye color. A study has been made of those belonging to the Suppressor 2 of zeste complex [Su(z)2-C]. The Su(z)2-C consists of at least three subregions called Psc (Posterior sex combs), Su(z)2 and Su(z)2D (Distal). The products of these subregions are proposed to act at the level of chromatin. Complementation analyses predict that the products are functionally similar and interacting. The alleles of Psc define two overlapping phenotypic classes, the hopeful and hapless. The distinctions between these two classes and the intragenic complementation seen among some of the Psc alleles are consistent with a multidomain structure for the product of Psc (Wu, 1995).

The DNA-binding protein encoded by the zeste gene of Drosophila activates transcription and mediates interchromosomal interactions such as transvection. The mutant protein encoded by the zeste1 (z1) allele retains the ability to support transvection, but represses white. Similar to transvection, repression requires Zeste-Zeste protein interactions and a second copy of white, either on the homologous chromosome or adjacent on the same chromosome. Two pseudorevertants of z1 (z1-35 and z1-42) were characterized, as well as another zeste mutation (z78c) that represses white. The z1 lesion alters a lysine residue located between the N-terminal DNA-binding domain and the C-terminal hydrophobic repeats involved in Zeste self-interactions. The z78c mutation alters a histidine near the site of the z1 lesion. Both z1 pseudorevertants retain the z1 lesion and alter different prolines in a proline-rich region located between the z1 lesion and the self-interaction domain. The pseudorevertants retain the ability to self-interact, but fail to repress white or support transvection at Ultrabithorax. To account for these observations and evidence indicating that Zeste affects gene expression through Polycomb group (Pc-G) protein complexes that epigenetically maintain chromatin states, it is suggested that the regions affected by the z1, z78c, and pseudorevertant lesions mediate interactions between Zeste and the Pc-G maintenance complexes. Because the DNA-binding domain of Zeste is unaffected by the z1-35 and z1-42 mutations, the data indicate that both repression of white and transvection require interactions other than Zeste-DNA and Zeste-Zeste interactions, and that these other interactions involve the proline-rich region. It is postulated that the proline-rich region interacts with other transcription factors to mediate repression and activation and that the region affected by the z1 and z78c lesions regulates these interactions (Rosen, 1998).

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Chen, J. D. and Pirrotta, V. (1993b). Multimerization of the Drosophila zeste protein is required for efficient DNA binding. EMBO J 12: 2075-83

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date revised: 20 December 2007

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