Recruitment to Chromatin of (GA)n-Associated Factors GAF and Psq in the Transgenic Model System Depends on the Presence of Architectural Protein Binding Sites.

Polycomb group (PcG) repressors and Trithorax group (TrxG) activators of transcription are essential for the proper development and maintenance of gene expression profiles in multicellular organisms. In Drosophila, PcG/TrxG proteins interact with DNA elements called PRE (Polycomb response elements). We have previously shown that the repressive activity of inactive PRE in transgenes can be induced by architectural protein-binding sites. It was shown that the induction of repression is associated with the recruitment of PcG/TrxG proteins, including the DNA-binding factors Pho and Combgap. In the present study, we tested the association of the two other PRE DNA-binding factors, GAF and Psq, with bxdPRE in the presence and absence of sites for architectural proteins. As a result, it was shown that both factors can be efficiently recruited to the bxdPRE only in the presence of adjacent binding sites for architectural proteins Su(Hw), CTCF, or Pita.

Sfmbt Co-purifies with Hangover and SWI/SNF-Remodelers in Drosophila melanogaster.

Polycomb group (PcG) proteins are chromatin-associated factors involved in the repression of gene transcription. In the present study, we characterized the interactome of the Sfmbt factor at the embryonic stage of development. For this, the Sfmbt protein complex was affinity purified from the nuclear extract, followed by highly specific peptide sequencing (IP/LC-MS). As a result, a number of previously uncharacterized Sfmbt interactions were discovered. In particular, Sfmbt top-interacting proteins include the DNA-binding protein Hangover and components of the SWI/SNF family of chromatin remodelers.

Polycomb and Trithorax Group Proteins: The Long Road from Mutations in Drosophila to Use in Medicine.

Polycomb group (PcG) and Trithorax group (TrxG) proteins are evolutionarily conserved factors responsible for the repression and activation of the transcription of multiple genes in Drosophila and mammals. Disruption of the PcG/TrxG expression is associated with many pathological conditions, including cancer, which makes them suitable targets for diagnosis and therapy in medicine. In this review, we focus on the major PcG and TrxG complexes, the mechanisms of PcG/TrxG action, and their recruitment to chromatin. We discuss the alterations associated with the dysfunction of a number of factors of these groups in oncology and the current strategies used to develop drugs based on small-molecule inhibitors.

[Control of the gene activity by polycomb and trithorax group proteins in Drosophila].

Combinatorial expression of the genes in multicellular organisms leads to the development of different cell types. The important epigenetic regulators of higher eukaryotes are the Polycomb group (PcG) and Trithorax group (TrxG) proteins. These factors control the transcription of a large number of genes involved in various cellular processes. Dysregulation of PcG and TrxG systems leads to developmental abnormalities and cancer. This review focuses on the main characteristics and properties of the Drosophila PRE elements. Furthermore, we summarize the information on the protein components of the PcG and TrxG groups and their functional activities and discuss the main aspects of competition between the proteins of these classes as well as their possible mechanisms of action.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster.

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesn't prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

[The Effect of Transcription on Enhancer Activity in Drosophila melanogaster].

In higher eukaryotes, the level of gene transcription is under the control of DNA regulatory elements, such as promoter, from which transcription is initiated with the participation of RNA polymerase II and general transcription factors, as well as the enhancer, which increase the rate of transcription with the involvement of activator proteins and cofactors. It was demonstrated that enhancers are often located in the transcribed regions of the genome. We showed earlier that transcription negatively affected the activity of enhancers in Drosophila in model transgenic systems. In this study, we tested the effect of the distance between the leading promoter, enhancer, and target promoter on the inhibitory effect of transcriptions of different strengths. It was demonstrated that the negative effect of transcription remained, but weakened with increased distance between the leading promoter and enhancer and with decreased distance between the enhancer and target promoter. Thus, transcription can modulate the activity of enhancers by controlling its maximum level.