Olga Simonova

Recent data obtained in the authors' laboratories concerning the behaviour of mobile genetic elements of Drosophila melanogaster are reviewed. It was found that the mobile element jockey represents the typical LINE element. It is efficiently transcribed in D. melanogaster cells in flies and in culture. Transcription is initiated from the +1 nucleotide of jockey and depends on an internal promoter. This is the first case of an internal promoter being used by RNA polymerase II. Several events which take place during the transposition bursts in ctMR2 family of strains were described. Among them are the removal of mobile dispersed genetics (mdg) elements (with solo long terminal repeat (LTR) remaining at the site of excision), complete removal of an mdg element, and reinsertion of the same mdg to the same place either in the presence or in absence of solo LTR sequence. Finally, the formation of deletions was observed. A 462-bp deletion destroying the white locus can be further repai...

To study the regulatory mechanism of the Aryl hydrocarbon receptor (AHR), target genes of transcription are necessary for understanding the normal developmental and pathological processes. Here, we examined the effects of human AHR ligands on male fecundity. To induce ectopic human AhR gene expression, we used Drosophila melanogaster transformed with human AhR under the control of a yeast UAS promoter element capable of activation in the two-component UAS-GAL4 system. We found that exogenous AHR ligands decrease the number of Drosophila gonadal Tj-positive cells. We also found both an increase and decrease of AHR target gene expression, including in genes that control homeostasis and testis development. This suggests that gonadal AHR activation may affect the expression of gene networks that control sperm production and could be critical for fertility not just in Drosophila but also in humans. Finally, we found that the activation of the expression for some AHR target genes depends ...

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR's target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of AHR in a living organism. Here, we examined the effects of human AHR and its ligands using transgeniclines with an inducible humangene. We found that exogenous AHR ligands can increase as well as decrease the transcription levels of the AHR target genes, including genes that control...

Leg-arista-wing complex (lawc) mutations affect the expression of D. melanogaster proteins homologous to a human basic transcription factor, TBP (TATA-box binding protein) Related Factor 2 (TRF2), specifically involved in development. The paper for the first time reports the application of genetic screens for various genomic regions to recover genetic interactions between the lawc/Trf2 gene and other genes and genetic loci by using Deficiency Kit lines with small deletions in total providing maximal coverage of the genome. The deletion mapping allowed us to recover 26 genomic regions that, when deleted, are lethal or modify the mutant phenotype due to a decreased TRF2 expression level. These deletions could be useful in identifying both novel TRF2 targets and its positive and negative regulators. There is evidence that TRF2 can be a component of high molecular DNA Replication-related Element Factor (DREF)- and Nucleosome Remodeling Factor (NURF)-containing complexes. The present stu...

Preliminary analysis of the leg-arista-wing complex (lawc) gene region in the corresponding mutants revealed P element insertion in the transcribed region of this locus. To demonstrate the main role of P element insertion in the complex pleiotropic phenotypic manifestation of the lawc gene, a system using P-Ph chimeric protein and based on the P-mediated repression of the lawc in vivo transcription was applied. As a result, extreme lawc-mutant phenotypes were obtained and examined. The P-Ph-mediated decrease of the level of the lawc gene transcription was also demonstrated.

Numerous studies showed that overlapping genes are fairly common elements of genome organization, not only in viruses and prokaryotes but also in eukaryotes. At the same time, the regulatory mechanisms of overlapping gene expression, as well as the functional relevance of antisense transcription, are still relatively unknown. This review describes the history of the discovery of regulatory antisense RNAs, the types of gene overlap, and the putative mechanisms of their functioning. In conclusion, the critical views of different authors on the problem of detecting overlapping genes and an evaluation of the level of antisense transcription are presented.

During crossing of two stable laboratory lines, y²sc/sup 1w/sup aG// and Df(1)Pgd-kz/FM4, y/sup 31d/sc⁸dm B, consistent instability originated reproducibly in progeny containing a y²sc¹w/sup aG/ chromosome and autosomes of both lines. It is expressed in active mutagenesis observed over the course of several tens of generations. Destabilization occurs independently of direction of crossing. Mutagenesis occurs both in somatic and in

Using a highly mutable FM/w oc system, we have established a new allele of ssa40aSc mutation whose phenotype is identical to ssa40aNs compound described in the literature. The following features are characteristic of the ssa40aSc flies phenotype: (1) the increased number of sex comb teeth, (2) complete fusion of tarsal segments, and (3) the decreased bristle size corresponding to that of ss flies. The first two features are evidence for the impaired stem cell proliferation in the antennal and leg imaginal discs which are determined to form distal structures. This assumption was experimentally confirmed when we transplanted leg imaginal discs from III instar larvae of different age into prepupae. The observed phenomenon is probably due to the defects of the Antp and Pc translation products binding site in the ss locus.

Phenotypic expression of mutations within the leg-aristal-wing complex (lawc) locus involves alteration of the number and location of macrochaetae. In Drosophila, development of macrochaetae depends on products of the two proneural genes, achaete (ac) and scute (sc), constituents of the approximately 90-kb ac-sc gene complex (AS-C). Untranscribed regions of AS-C involve enhancer-like cis-elements that are responsible for the local combination of some factors specifically determining expression of the ac-sc genes in larval imaginal discs of Drosophila. In the present work, the frequency of appearance of additional macrochaetae was tested to analyze phenotypic exhibition of the temperature-sensitive lawcp1 allele. This mutation was also genetically analyzed in combination with various AS-C alleles involving alterations of transcribed or cis-regulatory regions of this gene complex. A hypothesis that the lawc gene encodes a factor determining the specific expression of the ac-sc genes is discussed.

It is well established that taste chemoreceptors in Drosophila are located on the tarsi of the first leg pair. In order to investigate the influence of the novel homeotic arista-tarsus transformation on behavior, an analysis of taste perception in the lawc-mutants, characterized by the transformation of the arista into tarsus elements, was carried out. The data were subjected to thorough statistical treatment. It was shown that elements of an additional leg that appeared as a result of homeotic transformation of the arista were sensitive to gustatory stimuli. Analysis of the innervation of the homeotic organs by means of cobalt staining of afferent projections showed that the afferents starting from the homeotic leg reached the thoracic ganglion.

Antennae are known to be olfactory organs in Drosophila. The leg-aristae-wing complex (lawc) mutation causes a homeotic transformation of the arista (the fifth element of antenna) into tarsal elements. To test how the homeotic transformation of the arista into the tarsus can affect behavior, we studied the olfactory response in the lawc mutants. The data were carefully processed by statistical methods. In spite of a low penetrance of the trait of arista transformation, the mutant flies were found to be approximately half as perceptible to attractant odors than the wild-type flies.

Determination of the period of temperature sensitivity in the temperature-sensitive allele of the regulatory lawc(P1) mutation was performed. Homeotic transformation of arista into tarsus, frequency of leg deformation, and bristle superexpression were examined. The sensitive periods were detected using reciprocal changes of cultivation temperature from 28 to 17 degrees C and from 17 to 28 degrees C. The temperature-sensitive period (TSP) for arista transformation was shown to manifest polyphasic expression and sexual dimorphism. In females, it occurred in late third instar larvae (the first phase) and prepupae (the second stage); in males, it includes the whole period from the late third instar larva upto and including prepupa. TSP for the frequency of deformed legs was polyphasic and took place during the third larval instar (the first phase) and prepupa stage (the second one). TSP for bristle superexpression occurred during a single interval from the late third larval instar until the early prepupa stage. The products of the lawc gene are assumed to play a role both in the cell proliferation in the legs of antennal and imaginal discs and in the control of bristle expression at the final stages of Drosophila ontogeny.

ABSTRACT A family of closely related genes, named the d4 family, has been previously identified in mammals. It comprises three genes encoding structurally related proteins. The hallmark of the family is D4 domain—a double-paired finger motif that consists of two tandemly arranged PHD finger domains. These genes are expressed in various tissues and at various developmental stages. Two of those, neuro-d4 and cer-d4, are strictly neurospecific and their expression is developmentally regulated. Another gene, ubi-d4/Requiem is ubiquitously expressed in all embryonic and adult tissues at the same levels. d4 family genes are evolutionary conserved. Human, mouse, rat, and chicken d4 genes have been cloned. The only d4-like gene was found in the genome of nematode C. elegans and hydra H. magnipapillata. The sole member of d4 family was identified also in the genome of D. melanogaster. However, d4 genes are not believed to be present in the genomes of prokaryotes and yeast. This review describes genomic organization and expression of d4 family genes in vertebrates.

ABSTRACT The regulatory gene leg-arista-wing complex ( lawc ) of Drosophila is located in the region 7E7-11 of the X chromosome in. Mutations in the lawc gene induced by the insertion of a P element result in a pleiotropic phenotype: homeotic transformations and defects in different organs (transformation of the arista into the leg, underdevelopment of extremities, abnormalities in the development of the wings, and disturbance of the topology of bristles) [1‐3]. To determine gene function, it is crucial to obtain either completely inactivated or maximally abnormal alleles. In the world collection, strains with required mutations were absent. To obtain lethal mutations in the lawc gene, we used a modernized P‐M system of hybrid dysgenesis. We attempted to increase the efficiency and frequency of mutagenesis at the site of the P element location and to obtain as many structural rearrangements in this locus as possible. Obtaining lethal mutations. Mutagenesis was performed under the conditions of P‐M hybrid dysgenesis using the technique developed in our laboratory, which prevents break repair by the mechanism of homologous recombination or conversion after P element copy excision (Fig. 1a). The idea of the experiment consisted in destabilization of the P element in flies, one homologous X chromosome of which carried the P element inserted in the region of interest and the other had a break in the same or nearby region. In the lawc p1 mutant, the only potentially active copy of the P element was initially located in the lawc gene region [7E5-11], and the opposite chromosome had a break in the adjacent region [7E2-3] and a translocation at the site of break of arms of the Y chromosome ( T(1; Y)W31 ). Homozygous ct n lawc p 1 females were crossed with the w/Y; ∆ 2–3 , Sb/TM3 males. In the progeny obtained by this crossing (F1), the ct n lawc p1 /Y; ∆ 2–3 , Sb/+ males were selected and crossed with the T(1; Y)W31/FM7a females. To balance the X chromosome, in which a lethal mutation could

ABSTRACT A newly found locus of the Drosophila melanogaster genome, named toothrin (tth) has been used to study the role of the conserved the 2/3 domain of genes from the d4 family. In contrast to all vertebrates studied (including humans), in which the 2/3 domain is always accompanied by the d4 domain, the tth gene contains the sequence encoding the 2/3 domain but lacks that encoding the d4 domain. The tth gene overexpression has been studied using the two-component system UAS-GAL4. It has been demonstrated that the tth overexpression at the third-instar larval (prepupal) stage decreases survival rate, simultaneously causing a substantial deceleration of development in Drosophila. It is known that the change of developmental stages in Drosophila is controlled by the rates of the expression of ecdysteroid and juvenile hormones (JHs). It is supposed that the overexpression of the tth gene causes either a shift in the ecdysterone-to-JH ratio (through a decreased JH decay rate or a delayed initiation of ecdysone synthesis) or a deceleration of the release of ecdysterones synthesized.