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Biomedical subjects

P G Georgiev

Publications and source records attributed to P G Georgiev.

At least 19 recordsLinked to original sources

[Insulators of higher eukaryotes: properties, mechanisms of action, and role in transcriptional regulation].

One of the dogmas of transcriptional regulation in higher eukaryotes suggests the existence of transcriptional domains with no promoter-enhancer interactions between them. Specific regulatory elements, known as insulators, block the interaction between an enhancer and a promoter. Insulators are believed to act as transcription domain boundaries. The review considers general properties of well-known insulators identified in Drosophila and vertebrates. The mechanism of action of insulators and their role in the regulation of gene expression are discussed on the basis of available information.

Animals↗

[Cause for maintaining high instability at the yellow gene in Drosophila melanogaster lines, isolated during the "mode for mutation" period in Uman populations].

Mobile genetic elements are responsible for most spontaneous mutations in Drosophila melenogaster. The discovered in the 1980s phenomenon of frequent change of the wild-type yellow phenotype for a mutant one, and vice-versa, in strains of Drosophila melanogaster isolated from the Uman' natural population can be, according to our data, explained by repeated inversions and reinversions of the gene regulatory region located between the two copies of the hobo transport. However, most molecular genetic events accompanying the process can occur without the phenotype change. After several generations, the strains, remaining phenotypically unchanged, can possess different molecular genetic properties with respect to yellow. Using genetically homogenous or isogenic strains for the genetic analysis or for production of the new plant cultivars or animal breeds, geneticists and breeders often face the problem of stability of the strains. In the present study, the mechanism underlying the generation of instability at the yellow locus of D. melanogaster determined by the hobo-induced genome instability is described.

Animals↗

[Search for new regulatory elements of the Bithorax complex in Drosophila melanogaster].

The Ultrabithorax (Ubx), Abdominal-A (Abd-A), and Abdominal-B (Abd-B) homeotic genes of the Bithorax complex are responsible for the development of body segments in Drosophila melanogaster. Their regulatory region of approximately 300 kb harbors a series of specific enhancers, each regulating expression in a single parasegment. Molecular genetic analysis of the Abd-B gene revealed the regulatory modules MCP, Fab-7, and Fab-8, which contain insulators with adjacent silencers. The present work was aimed at searching for similar regulatory elements in the promoter regions of the Abd-A and Abd-B genes and new regulatory modules in the Abd-B gene region. Four DNA fragments, each containing numerous specific sequences characteristic of regulatory modules, were tested for the ability to suppress transcription of the yellow and white genes and for the interaction with MCP. The DNA fragment of the Abd-A promoter region proved to act as an effective silencer. The fragment of the iab4 domain showed insulator properties. The fragment of the Abd-B promoter region interacted with MCP in providing for communication between the enhancer and promoter of the white gene.

Animals↗

[Roles of silencers from the regulatory region of the abdominal-B gene and the Zw5 and Su(Hw) insulators in regulating gene expression in Drosophila melanogaster].

A study was made of the functional role of silencers in the long-distance interaction between insulators. Transgenic lines containing the Su(Hw) and Zw5 insulators were analyzed. The silencers failed to efficiently suppress transcription of the yellow gene, nor did they neutralize the effect of the Su(Hw) insulator. The long-distance interaction between insulators was assumed to depend on the combined effects of silencers, insulators, and, possibly, some unidentified regulatory elements.

Animals↗

[Nuclear protein e(y)2 from Drosophila melanogaster participates in transcription control].

Molecular analysis of a new evolutionarily conserved transcription factor, e(y)2, was carried out. The protein was detected in a complex of approximately 700 kDa contained in a Drosophila melanogaster transcription nuclear extract. The e(y)2 protein was shown to interact with components of the preinitiation transcription complex TFIID. Addition of e(y)2 to a transcription extract of HeLa cells increased transcription 4-5 times when chromatin, but not free DNA, was used as a template. Genetic analysis showed that the C-terminal amino acid residues of transcription factor TAFII40 are important for its interaction with e(y)2.

Animals↗

["Mode for mutation" in the natural population of Drosophila melanogaster from Umani is caused by distribution of a hobo-induced inversion in the regulatory region of the yellow gene].

A mutation outburst of the yellow gene occurred in a Drosophila melanogaster population from the town of Uman' from 1982 to 1991 and was associated with the instability of several alleles. Molecular genetic analysis revealed a deletion variant of the hobo transposable element in the same site of the regulatory region of yellow in the mutant alleles and their derivatives. The outburst of the yellow-2 mutations was attributed to the spreading of the X chromosome, which contained an inversion of the yellow regulatory region, through the population. Reinversion resulted in the wild-type phenotype. Crossing lines carrying the inversion with laboratory line C(1)DX, ywf induced instability of the yellow alleles, which was associated with duplication or multiplication of a fragment of the yellow gene. Most derivative lines eventually became stable. The loss of instability was not associated with phenotypic changes; molecular genetic changes included a loss of the duplicated sequences or a deletion of the inverted regulatory region of the yellow gene.

Animals↗

[Model genetic system for analysis of attachment of HeT-A elements to terminal deletions in Drosophila melanogaster].

Telomeres of Drosophila consist of multiple copies of LINE-like transposable elements. These elements are assigned to two classes, HeT-A and TART. They are attached to terminal deletions at their 3' end, thus compensating for the absence of telomerase in Drosophila cells. The attachment of HeT-A elements to the X-chromosome terminal deletions of the regulatory region of the yellow gene was studied. It was shown that, in the case of degradation of the yellow promoter sequence (chromosome underreplication), the Het-A promoter located at the 3' end of this element can activate transcription of the gene. The minimal size of the 3'-end HeT-A element sequence sufficient for the yellow expression was shown to be 400 bp. Since the yellow mutation is expressed phenotypically and the gene impairment is not lethal, we created a convenient model genetic system based on this effect. Using this system, the frequency of attachments of the HeT-A elements to the chromosome end can be visually recorded. This frequency varied in a wide range (from 0.2 x 10(-4) to 2 x 10(-3)) and was strain-specific.

Animals↗

[The role of P-element sequences in the transcription activation].

A study was made of mutations resulting from insertion of the P element in the regulatory region of the yellow gene. Excision of the P element enhanced expression of yellow. Molecular analysis implicated P-element terminal sequences, which remained in the locus after the element was excised, in transcription activation of the yellow gene.

Animals↗

[Insulators and interaction between long-distance regulatory elements in higher eukaryotes].

Enhancers can activate a promoter located as far as several hundred kilobases away, which is specific for transcription regulation in higher eukaryotes. Notwithstanding the vast information accumulated on transcription regulation at various levels, the mechanism of long-distance enhancer-promoter interactions is still obscure. Modern views of insulators as elements modulating enhancer-promoter interactions are reviewed.

Enhancer Elements, Genetic↗

[Mechanisms of excising the P-element in a model system at the yellow locus of Drosophila melanogaster].

Patterns of excision of a single P element were studied in a model system of the yellow locus. The data obtained were in good agreement with the generally accepted SDSA (synthesis-dependent strand annealing) model. Specific features of P element excision in the presence of two tandemly repeated copies are presented. The pattern of P element excision depended on the sequences surrounding the insertion site and on the number of its additional copies present in the genome.

Animals↗

[Role of the "enhancer of yellow" genes in the regulation of expression of the "yellow" gene in Drosophila melanogaster].

The e(y)1/TAFII40, e(y)2 and e(y)3 genes encode general transcription factors in Drosophila melanogaster. Weak mutations in e(y)1u1, e(y)2u1 and e(y)3u1 regulate enhancer-dependent transcription of the yellow gene in bristles similarly, even if it is activated by a non-yellow specific enhancer element. At the same time, these mutations do not affect yellow expression in the body and wings. We found genetic data indicating that the e(y) proteins support the promoter/bristle enhancer interaction. Futhermore, the su(Hw) insulator properties change in the presence of e(y)1u1, e(y)2u1 and e(y)3u1 mutations. When introduced at +2490 from the transcription initiation site, the su(Hw) insulator becomes able to block interactions between the bristle enhancer and yellow promoter, not separating them from each other.

Animals↗

[Analysis of the interaction of mutations at the Drosophila melanogaster Su(mg), mod(mdg4), and su(Hw) loci].

The mod(mdg4)1u1 mutation modifies the phenotypic expression of mutations induced by the MDG4 insertion. The Suppressor of modifier mdg4 (Su(mg)) gene family was described earlier. Most Su(mg) mutations completely suppressed the negative effect of the mod(mdg4)1u1 mutation on transcription of the yellow gene. However, only a few Su(mg) mutations suppressed the inhibiting effect of mod(mdg4)1u1 on transvection between the y59b/y2 alleles. The interaction of the mod(mdg4) and Su(mg) mutations with the su(Hw) mutation was studied. The phenotypic expression of the Su(mg) and mod(mdg4)1u1 mutations was shown to depend on the presence of the functional protein su(Hw).

Alleles↗

[Isolation and genetic analysis of double hyperunstable systems in Drosophila melanogaster].

Hyperunstable mutations were described previously at the yellow locus of Drosophila melanogaster. These mutations are related to the insertion of the complex sequence containing two deleted copies of the P element at the termini and central unique regions from different sites of the X chromosome. In this work, double hyperunstable mutations at loci yellow and scute were obtained. These events were shown to occur from the inversion induced by the P elements located at the loci yellow and scute.

Alleles↗