[Molecular components of JAK/STAT signaling pathway and its connection with transcription machinery].

JAK/STAT is one of the conservative signaling pathways in higher eukaryotes which plays a critical role in different ontogenesis processes. This article gives a review of the pathway structure at the molecular level, mainly in a model organism Drosophila. There are data about relationship of the signaling pathway and transcription machinery of higher eukaryotes.

[Activation of JAK/STAT signaling pathway in S2 Drosophila melanogaster cell culture].

JAK/STAT signaling pathway plays a critical role in different ontogenesis processes of higher eukaryotes. Fruit fly drosophila is a handy model system used to study this pathway since major components of the pathway are represented by unique factors. This article describes the usage of Drosophila melanogaster S2 cells in studies of the pathway's target genes activation. We showed that S2 cells contain plenty of STAT protein which migrates into nucleus under cells treatment with pervanadate. Then we demonstrated that under pervanadate action STAT protein along with other transcription factors is recruited onto regulatory sequences of target genes and activates their transcription.

[SAYP interacts with DHR3 nuclear receptor and participates in ecdysone-dependent transcription regulation].

The role of metazoan coactivator SAYP in nuclear receptor-driven gene activation in the ecdysone cascade of Drosophila is considered. SAYP interacts with DHR3 nuclear receptor and activates the corresponding genes by recruiting the BTFly (Brahma and TFIID) coactivator supercomplex. The knockdown of SAYP leads to a decrease in the level of DHR3-activated transcription. DHR3 and SAYP interact during development and have multiple common targets across the genome.

[Functioning of macromolecular complexes at successive stages of gene expression as self-coordinated molecular machines].

The results of systemic investigations devoted to the role of the proteins SAYP and ENY2 from Drosophila melanogaster in the regulation of different stages of gene expression are presented. The gene expression is a system of multistage processes involving the preparation of the chromatin matrix, initiation of transcription, mRNA synthesis, as well as the formation of mPNR particles, their export, and translation in the cytoplasm. At each of these stages, a great number of factors present6ed usually by protein complexes consisting of different subunits work. An analysis of the available evidence indicated that the transcription coactivators SAYP and ENY2 act in gene expression as cooperative nanoregulators, thereby determining the molecular mechanisms of coordination of spatial and temporal characteristics of the processes involved in the realization of genetic information.

[Novel conservative domain of SAYP coactivator mediates TFIID and Brahma transcriptional complexes interaction].

In the S2 cell system of Drosophila melanogaster a key protein domain mediating the interaction of TFIID and Brahma transcriptional complexes into the BTFly supercomplex has been shown to be an evolutionary conserved SAY domain of the SAYP. TFIID and Brahma coactivators participated in the reporter gene activation induced by the SAY domain in cellular nuclei. The TFIID and Brahma components directly interacting with the SAY domain were identified.

[SAYP--a novel regulator of metazoan development].

SAYP is a dual-function transcriptional coactivator of RNA polymerase II. It is a metazoan-specific factor involved in different signaling pathways that control normal development. In Drosophila, SAYP is present in the organism from the early stages of development and participates in cell cycle synchronization at the blastoderm stage. SAYP is abundant in many embryonic cells and in imaginal discs of larvae and is crucial for oogenesis in adults. At the molecular level, SAYP serves as a basis for assembling the BTFly nuclear supercomplex consising of the Brahma and TFIID coactivators. We suppose that BTFly and other similar nuclear supercomplexes play an important role in ontogenesis.

[Multifunctional factor ENY2 integrates the various stages of gene expression].

The ENY2/Sus1 is a multifunctional transcription factor which couples transcription with mRNA export. It is the component of the SAGA/TFTC and TREX-2/AMEX protein complexes. Recently, we described the interaction of ENY2 with one more protein complex, THO. Moreover, our data indicate that ENY2 associates with other nuclear and cytoplasmic factors. Thus, being the component of a number of protein complexes, ENY2 plays the role of an adaptor molecule, involved into the integration of different cellular processes, specifically, subsequent stages of gene expression.

[Conservative E(y)2/Sus1 protein is the member of SAGA complex and new nuclear pore-associated complex in Drosophila].

The SGA/TFTC complex plays an important role in the regulation of transcription. We have examined the significance of the gene positioning in the nucleus for its transcription and subsequent export of nascent mRNA. It was demonstrated that E(y)2 protein was a subunit of the SAGA/TFTC histone acetyl transferase complex in Drosophila and that E(y)2 concentrated at the nuclear periphery. An interaction between E(y)2 and the nuclear pore complex (NPC) was demonstrated, as well as that SAGA/TFTC also contacted the NPC at nuclear periphery. In addition, it was shown that E(y)2 formed complex with the Xmas-2 protein (X-linked male sterile 2) both in normal conditions and after heat shock. Importantly, the E(y)2 and Xmas-2 knockdown decreased the contact between the heat-shock protein 70 (hsp70) gene loci and the nuclear envelope before and after activation, and interfered with the transcription. Thus, E(y)2 and Xmas-2 together with SAGA/TFTC functioned in the anchoring of a subset of transcription sites to the NPCs to achieve efficient transcription and mRNA export.

[Novel complex, formed by transcription coactivator SAYP].

The multisubunit complex which contains the novel evolutionarily conservative transcription factor SAYP was isolated and the protein composition of the complex was determined. It was shown that SAYP unites two complexes with different functions in transcription activation: the chromatin - remodeling complex PBAP (SWI/SNF) and the main component of preinitiation complex of Pol II, general transcription factor TFIID. The isolated super-complex contained the full set of PBAP and TFIID subunits. All components of supercomplex (SAYP, TFIID and PBAP) are essential for its effective interaction with promoters of SAYP-dependent genes.

[Study of the Drosophila melanogaster trf2 gene and its protein product].

The Drosophila melanogaster TRF2 protein regulates transcription of several genes. The trf2 gene structure was studied. The gene proved to code for two protein isoforms, a known 75-kDa isoform and a newly identified 175-kDa isoform. The new isoform combines the known isoform sequence with an extended N end containing a coiled-coil motif. The long TRF2 isoform was found to act as a component of a multiprotein complex, including ISWI ATPase as well.

[Principles of functioning of the complex of transcription initiation by RNA polymerase II].

This final review describes the general principle and mechanisms that underlie functioning of the machinery of transcription initiation by polymerase II in eukaryotes. The main models of transcription initiation, the module principle underlying the structure of the transcription complex, the regulation of transcription initiation, and the association between the nuclear architecture and transcription are discussed.

[The effect of chromatin remodeling and modification on RNA-polymerase-mediated transcription initiation].

As eukaryotes are characterized by the presence of chromatin (intricately packaged DNA), special mechanisms are required for preparing the DNA template for operation of the transcription machinery. Recently, a close association between the chromatin state and transcription was found and numerous transcription factors modifying the physical and chemical chromatin state were revealed. This review presents a brief description of transcription initiation on the DNA template within chromatin.

[Transcriptional coactivator SAYP can suppress transcription in heterochromatin].

The new transcriptional coactivator SAYP binds at many sites to transcriptionally active chromatin of polytene chromosomes, colocalizes with RNA polymerase II, and coactivates transcription. On the other hand, SAYP is present in heterochromatic regions of chromosome IV and in the chromocenter and suppresses transcription of transgenes located in heterochromatin. The conserved SAY domain of SAYP is involved in transcription activation, while its PHD domains are responsible for gene silencing in heterochromatin. Thus, SAYP plays a dual role in regulating transcription in euchromatic and heterochromatic regions.

[Molecular machinery of the transcription initiation by RNA polymerase II].

Transcription is the first stage of the realization of genetic information. In recent years, substantial progress in understanding of this process has been achieved. Eukaryotic cell nuclei were shown to possess extremely complex transcription machinery consisting of more that a hundred different factors. A series of our reviews is devoted to the first step of the transcription process, which is of key significance for the control of gene expression: transcription initiation on the genes transcribed by RNA polymerase II. This paper gives a short description of the main factors involved in this process.