[Transcription factor comr acts as a direct activator in the genetic program controlling spermatogenesis in D. melanogaster].

Cardiff University, Cardiff CF10 3AX, UK). In Drosophila melanogaster differentiation of the male germ cells is accompanied by chromatin rearrangement and activation of the specific genes. These processes are regulated by few transcription factors that belong to two classes, can and aly that form distinct functional complexes. Mechanisms of action of aly and can class transcription factors on gene expression and chromatin state remain unclear. To investigate this question we have built the whole genome binding profile of transcription factor Comr belonging to aly class using the tissue-specific DamID method. Resulting datawere correlated with gene expression in comr (aly class) and can (can class) mutant testes. It was shown that Comr is a direct activator for about 300 testis-specific genes. Furthermore a set of genes revealed decreased expression in comr mutants but did not bind Comr protein, suggesting the existence of secondary regulation. Indeed, among the Comr gene targets we found a gene coding an uncharacterized transcription factor that could be a secondary participant in the genetic pathway in spermatocytes. These date allowed us to advance a model of gene activation needed for male gametes differentiation in D. melanogaster.

[A genetic system for somatic and germinal lineage tracing in the Drosophila melanogaster gonads].

Significant progress in the developmental biology of Drosophila is largely due to the improvement of methods of genetic manipulation and, in particular, development of ways to create mosaic organisms. The main characteristic of the mosaic organisms is the presence of genetically different populations of cells. For example, some tissues express a transgenic reporter gene that is absent in other cells of the body. This principle is used in a variety of the methods with the common name lineage tracing. The essence of these approaches is to perform the targeted changes in the genetic apparatus of progenitor cells that give rise to cell lines or organs and tissues. Genetic modification in progenitor cells, such as the ability to express a fluorescent protein, will be inherited by the next cell generations, and, as a result, the entire cell line or tissue will have a tag, which distinguishes it from the rest of the body. The lineage tracing methods allow tracking the cell generations, studying the cell proliferation process, tracing their origin and investigating the function of genes of interest in the development of a single tissue or organ. We have designed an approach to selectively label germ line or somatic cells in the gonads of Drosophila.

[Domain regulation of gene expression in the intercalary heterochromatin of Drosophila melanogaster].

A significant part of Drosophila genome is repressed in most cells. These areas, called intercalary heterochromatin regions, contain a significant amount of genes. Most of these genes work in well-defined cell types, that is, are tissue-specific. The most numerous class of genes in the intercalary heterochromatin are testis-specific genes. These genes are activated only in maturing spermatocytes and their coordinated activation is necessary for the normal spermatogenesis. Our work aims to study the mechanism of activation of testis-specific genes. We have found that Comr, one of the factors required for their transcription, is associated with extensive regions of chromosomes, which are often coextensive with the repressed parts of the salivary glands chromosomes. However, Comr binding to the large chromatin domains leads to the selective activation of testis-specific genes only. Our results suggest that, at the initial stages, activation of the testis-specific genes involves the entire domains of intercalary heterochromatin.

[Intercalary heterochromatin in the genome of Drosophila].

The modern concept of intercalary heterochromatin as polytene chromosome regions exhibiting a number of specific characteristics is formulated. DNA constituting these regions is replicated late in the S period; therefore, some strands of polytene chromosomes are underrepresented; i.e., they are underreplicated. Late-replicating regions account for about 7% of the genome; genes are located there in clusters of as many as 40. In general, the gene density in the clusters is substantially lower than in the main part of the genome. Late-replicating regions have an inactivating capacity: genes incorporated into these regions as parts of transposons are inactivated with a higher probability. These regions contain a specific protein SUUR affecting the rate of replication completion.

[Distribution of induced chromosome rearrangement breakpoints along the chromosome length and the problem of intercalary heterochromatin in Drosophila melanogaster].

Historically, the term "intercalary heterochromatin" was based on the finding that induced chromosome rearrangements occur at a higher frequency in the corresponding regions. The available molecular genetic data and, in particular, the results of the Drosophila Genome Project made it possible to decide between two possible explanations of the preferential location of chromosome rearrangement breakpoints in intercalary heterochromatin regions. Namely, a higher frequency of radiation-induced rearrangements in these regions correlates with the DNA content and probably lacks an association with the features of chromatin organization.

[Contribution of the SuUR gene to the organization of epigenetically repressed regions of Drosophila melanogaster chromosomes].

A significant portion of a eukaryotic genome is silent (epigenetically repressed). In Drosophila melanogaster, this portion includes mainly regions of pericentric and intercalary heterochromatin and euchromatin regions subject to position-effect variegation. Detailed study of the organization of intercalary heterochromatin regions of Drosophila melanogaster polytene chromosomes started from the discovery of the SuUR gene (Suppressor of UnderReplication). The ability of the SuUR mutation to suppress underreplication in intercalary heterochromatin regions was used for molecular tagging of these regions. We showed that underreplicated intercalary heterochromatin regions contained silent unique genes and retained the features of late replication and transcriptionally inactive chromatin state in various cell types. Over 50% of these regions contain unique genes clustered on the base of coordinated expression. The origin of clusters and putative mechanisms of their gene expression are discussed. Data on the SuUR gene, its expression, and effect on polytene chromosome structure and replication are summarized.