C2H2 Zinc Finger Proteins: The Largest but Poorly Explored Family of Higher Eukaryotic Transcription Factors.

The emergence of whole-genome assays has initiated numerous genome-wide studies of transcription factor localizations at genomic regulatory elements (enhancers, promoters, silencers, and insulators), as well as facilitated the uncovering of some of the key principles of chromosomal organization. However, the proteins involved in the formation and maintenance of the chromosomal architecture and the organization of regulatory domains remain insufficiently studied. This review attempts to collate the available data on the abundant but still poorly understood family of proteins with clusters of the C2H2 zinc finger domains. One of the best known proteins of this family is a well conserved protein known as CTCF, which plays a key role in the establishment of the chromosomal architecture in vertebrates. The distinctive features of C2H2 zinc finger proteins include strong and specific binding to a long and unique DNA recognition target sequence and rapid expansion within various animal taxa during evolution. The reviewed data support a proposed model according to which many of the C2H2 proteins have functions that are similar to those of the CTCF in the organization of the chromatin architecture.

I-SceI endonuclease, a new tool for studying DNA double-strand break repair mechanisms in Drosophila.

As a step toward the development of a homologous recombination system in Drosophila, we have developed a methodology to target double-strand breaks (DSBs) to a specific position in the Drosophila genome. This method uses the mitochondrial endonuclease I-SceI that recognizes and cuts an 18-bp restriction site. We find that >6% of the progeny derived from males that carry a marker gene bordered by two I-SceI sites and that express I-SceI in their germ line lose the marker gene. Southern blot analysis and sequencing of the regions surrounding the I-SceI sites revealed that in the majority of the cases, the introduction of DSBs at the I-SceI sites resulted in the complete deletion of the marker gene; the other events were associated with partial deletion of the marker gene. We discuss a number of applications for this novel technique, in particular its use to study DSB repair mechanisms.

hobo Induced rearrangements in the yellow locus influence the insulation effect of the gypsy su(Hw)-binding region in Drosophila melanogaster.

The su(Hw) protein is responsible for the insulation mediated by the su(Hw)-binding region present in the gypsy retrotransposon. In the y2 mutant, su(Hw) protein partially inhibits yellow transcription by repressing the function of transcriptional enhancers located distally from the yellow promoter with respect to gypsy. y2 mutation derivatives have been induced by the insertion of two hobo copies on the both sides of gypsy: into the yellow intron and into the 5' regulatory region upstream of the wing and body enhancers. The hobo elements have the same structure and orientation, opposite to the direction of yellow transcription. In the sequence context, where two copies of hobo are separated by the su(Hw)-binding region, hobo-dependent rearrangements are frequently associated with duplications of the region between the hobo elements. Duplication of the su(Hw)-binding region strongly inhibits the insulation of the yellow promoter separated from the body and wing enhancers by gypsy. These results provide a better insight into mechanisms by which the su(Hw)-binding region affects the enhancer function.

[Molecular analysis of a double hyperunstable system y(2ns)sc(me)]. / Molekuliarnyi analiz dvoinoi supernestabil'noi sistemy y(2ns)sc(me).

Molecular analysis of hyperunstable mutations in the adjacent yellow and scute loci was performed in a Drosophila melanogaster strain y2ns scme obtained earlier. The y2ns scme combination originated from the original y+ns mutation associated with the insertion into the regulatory region of the yellow gene of a chimeric sequence flanked by deletion copies of the P element. The new combination of mutations resulted from an inversion between P-element copies located in the adjacent yellow and scute loci. The inversion was flanked by two P-element copies at one side and one copy at the other side. All three P-element copies had various internal deletions and, therefore, could not code for active transposase. An introduction of the delta (2-3) gene for transposase induced mutagenesis in the y2ns scme strain. Most mutations observed were associated with either excision of a single P-element copy or reinversion resulting from the recombination between the ends of P elements located in the yellow and scute genes. Genetic analysis showed that the alleles resulting from the recombination at a high frequency reverted to the original state.

[Induction of single transpositions of mobile genetic elements in Drosophila melanogaster using mitomycin C]. / Induktsiia odinochnykh transpozitsii mobil'nykh geneticheskikh élementov u Drosophila melanogaster s pomoshch'iu mitomitsina C.

Intraperitoneal injections of mitomycin C into the males from laboratory strains of Drosophila melanogaster induce several mutation events in different loci of the X-chromosome in the offspring. These mutations are caused by transposition of mobile genetic elements. The transpositions are single and are not associated with transposition explosions.

[Superunstable systems in Drosophila melanogaster. Analysis of mutations in signed and cut loci]. / Supernestabil'nye sistemy u Drosophila melanogaster. Analiz mutatsii v lokusakh signed i cut.

The lines of the M'-cytotype characterized by a long-term instability (which was shown to be conditioned by transpositions of the new mobile element, Stalker) were hybridized with the P-line. This resulted in the appearance of a number of superunstable mutations at the yellow, white, singed, ocelliless and some other loci. The authors analyzed four independently obtained families of superunstable mutations at the singed locus. A wide spectrum of derivatives and high frequency of mutations were demonstrated, as well as the regularities of allelic transitions. Besides this, mutagenesis at the cut locus was observed in the chromosomes carrying sn mutations with frequency of 5.05 x 10(4). By means of the blot analysis it has been shown that most of ct mutations are intragenic deficiencies, ranging from 1.3 to 3 Kb, whose appearance is, conceivably, attributed to the inaccuracy of the insertion excision (the insertion is present but fails to alter the phenotype) at the cut locus of the chromosomes with the superunstable sn-alleles. In the lines with the sn- and ct-mutations the transpositions of the P-element and the Stalker were found, which indicates their involvement in mutagenesis. The authors discuss possible effects of inserting the complicated constructions, based on the combinations of P-element and the Stalker, on the induction of superinstability.

[Transpositional bursts and chromosome rearrangements in unstable lines of Drosophila]. / Transpozitsionnye vzryvy i khromosomnye perestroiki v nestabil'nykh liniiakh drozofily.

The phenomenon of transpositional bursts-massive simultaneous transpositions of mobile elements belonging to different structural classes and accompanied by multiple mutagenesis were earlier described. Although the mechanisms of this phenomenon are still unclear, it is obvious now that it embraces total genome and includes not only transpositions of different mobile elements but also recombination processes--homologous recombination for LTR's and gene conversion. It is shown in this work that transpositional bursts may be accompanied by appearance of grass chromosomal rearrangements. The chain of closely related mutations which is characterized, as well as pedigrees described earlier, by coordinated mutational transitions and multiple transpositions of mdg1, mdg2 and retrotransposon jokey was analyzed. Spontaneous appearance of mutations in the loci yellow, white (deficiency for 462 kb) and cut (insertion of mdg4, together with jokey) correlates with appearance of inversion In(I), 14A-20B, and the reversions of these mutations to the wild type (y+w+ct+) or to other alleles (ctMR2--insertion of mdg4 without jokey) are accompanied by reversions of inversion. The relationship of all lines analyzed in this work as well as the lines from other pedigrees was proved using analysis of polymorphic restriction sites at the scute and cut loci (5 probes were used). All "y w ctpN"--type mutants are shown to have insertion of about 7 kb at the scute locus which causes no alteration of phenotype. This once again proves multiple and coordinated character of changes taking place during hybrid dysgenesis.

[Clinical picture, diagnosis and treatment of metastatic melanoma of the brain]. / Klinika, diagnostika i lechenie metastaticheskikh melanoma golovnogo mozga.

The morphological and clinical features of the disease were studied in 73 patients with malanoma metastasis to the brain. A morphological examination revealed predominance of the epithelial-like structure of the tumors over fusocellular, infiltrative growth of metastases in the brain, and many newly formed defective vessels in the metastatic tumors which were conducive to frequent hemorrhages. The clinical picture of the disease was marked by the predominance of general cerebral symptoms over focal. With regard to the diagnosis, much importance is attached to medical history and peculiarities of the clinical manifestations of the disease and to the results of an auxiliary examination (radiocontrast, electrophysiological, etc). Treatment of patients with melanoma metastases in the brain should be combined and should include, whenever indicated, surgical intervention, hormonotherapy, radiotherapy, and chemotherapy.

[The content of somatotropic hormone and prolactin in the blood of patients with brain meningiomas]. / Soderzhanie somatotropnogo gormona i prolaktina v krovi bol'nykh meningiomami golovnogo mozga.

The content of somatotropic hormone and prolactin was assessed in patients with cerebral meningiomas. It was established that patients harbouring meningiomas of the cerebral hemispheres showed a high content of prolactin indicating hormone dependence of this tumour. The level of somatotropic hormone in meningiomas was insignificantly elevated.

[Thromboembolism of the pulmonary arteries after the removal of meningiomas of the cerebral hemispheres]. / Tromboémboliia legochnykh arterii posle udaleniia meningiom bol'shikh polusharii.

The authors describe and analyse a grave postoperative complication in neuro-oncological patients, namely pulmonary artery thromboembolism which is almost always lethal. Predisposing factors of pulmonary artery thromboembolism and clinical manifestations of this complication are discussed. It is concluded that prophylactic measures against thromboembolism in all patients with meningiomas of the brain in the postoperative period are of importance.

[Adrenal hemorrhage following the removal of meningiomas of the cerebral hemispheres]. / Krovoizliianie v nadpochechniki posle udaleniia meningiom polusharii bol'shogo mozga.

Adrenal apoplexy was revealed in 14.6% of the patients, who died after removal of meningiomas of the cerebral hemispheres. This complication more often occurred in basal location of a tumor. Manifestation of acute adrenal apoplexy in the majority of neurooncologic patients are atypical because of their general severe state after removal of a tumor. Adrenal apoplexy usually was associated with hemorrhagic and ischemic disorders in the central nervous system and internal organs and led to the death of patients. A search for the methods of investigation, permitting to prognosticate this complication is necessary.

[Gastrointestinal hemorrhage after removal of brain tumors]. / Zheludochno-kishechnoe krovotechenie posle udaleniia opukholei golovnogo mozga.

The diagnosis of gastrointestinal bleeding after the removal of a brain tumor is very difficult due to the severity of the state of the patients. Treatment of the bleeding is effective only in influencing both its source and the higher vegetative centers.

[Acute disorders of adrenal function in supratentorial meningioma]. / Ostrye narusheniia funktsii nadpochechnikov pri meningiome supratento- rialnoi lokalizatsii.

Of the 128 patients operated on for meningioma of supratentorial location in 52 (23.9%), hemorrhage into the adrenal tissue was revealed. Clinical diagnosis of this pathology is difficult. Pathogenetically, hemorrhage into the adrenal tissue should be considered as manifestation of generalized vascular disorders in complicated postoperative course, which are associated with significant functional strain of the endocrine system resulting from stress reactions.

[Cyclic nucleotides in patients with brain meningiomas]. / Tsiklicheskie nukleotidy u bol'nykh s meningiomami golovnogo mozga.

A study is presented of cyclic nucleotides--adenosinmonophosphate and guanosinmonophosphate in patients with meningiomas of the brain. It was established that adenosinmonophosphate and guanosinmonophosphate is characterized by an increased content in patients with brain meningiomas. This indicates disorders of proliferative processes in the body and changes on the cellular level.

Intragenic suppression: Stalker, a retrovirus-like transposable element, can compensate for a deficiency at the cut locus of Drosophila melanogaster.

A number of mutations at the cut locus were induced by non-precise excision of a silent P-element insertion which resulted in deletions at the regulatory region of the locus. Unexpectedly, a reversion of one of these mutations was found, which appears as a result of insertion of Stalker (a retrovirus-like mobile element) near the 1.3 kb deletion. Thus an insertion of a retrovirus-like mobile element can suppress the deficiency at the regulatory region of a gene.