A5018014073- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Chromosomal and Genetic Variations
- Plant Molecular Biology Research
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Neurobiology and Insect Physiology Research
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Animal Behavior and Reproduction
- Developmental Biology and Gene Regulation
- Protist diversity and phylogeny
- Chromatin Remodeling and Cancer
- Histone Deacetylase Inhibitors Research
- Animal Genetics and Reproduction
- Invertebrate Immune Response Mechanisms
- Cancer Genomics and Diagnostics
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Protein Degradation and Inhibitors
- Biochemical Analysis and Sensing Techniques
- Genomics and Phylogenetic Studies
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
Institute of Gene Biology
2016-2025
Russian Academy of Sciences
2009-2024
Although cancer initiation and progression are generally associated with the accumulation of somatic mutations
Abstract We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 its paralog CDK19, alternative enzymatic components the kinase module associated with transcriptional Mediator complex implicated in development diseases. This was performed using genetic modifications selective CDK8/19 small molecule inhibitors potent PROTAC degrader. inhibition cells exposed to serum or agonists NFκB protein C (PKC) reduced induction signal-responsive genes, indicating...
The Drosophila GAGA factor (GAF) has an extraordinarily diverse set of functions that include the activation and silencing gene expression, nucleosome organization remodeling, higher order chromosome architecture mitosis. One hypothesis could account for these activities is GAF able to interact with partners have specific dedicated functions. To test this possibility we used affinity purification coupled high throughput mass spectrometry identify associated partners. Consistent interacting...
In Drosophila, Polycomb (PcG) and Trithorax (TrxG) group proteins are assembled on response elements (PREs) to maintain tissue stage-specific patterns of gene expression. Critical coordinating expression with the process differentiation, activity PREs can be switched "on" "off." When on, PRE imposes a silenced state genes in same domain that is stably inherited through multiple rounds cell division. off, permissive for inherited. Previous studies have suggested burst transcription sequence...
Abstract Background Epigenetic memory plays a critical role in the establishment and maintenance of cell identities multicellular organisms. Polycomb trithorax group (PcG TrxG) proteins are responsible for epigenetic memory, flies, they recruited to specialized DNA regulatory elements termed polycomb response (PREs). Previous transgene studies have shown that PREs can silence reporter genes outside their normal context, often by pairing sensitive (PSS) mechanism; however, silencing activity...
AbstractThe Drosophila TATA box-binding protein (TBP)-related factor 2 (TRF2 or TLF) was shown to control a subset of genes different from that controlled by TBP. Here, we have investigated the structure and functions trf2 gene. We demonstrate it encodes two isoforms: previously described 75-kDa TRF2 newly identified 175-kDa version in which same sequence is preceded long N-terminal domain with coiled-coil motifs. Chromatography embryo extracts revealed part multiprotein complex also...
Chromatin insulators are regulatory elements involved in the modulation of enhancer-promoter communication. The 1A2 and Wari located immediately downstream Drosophila yellow white genes, respectively. Using an assay based on yeast GAL4 activator, we have found that both able to interact with their target promoters transgenic lines, forming gene loops. existence insulator-promoter loop is confirmed by fact insulator proteins could be detected promoter only presence transgene. upstream...
Abstract Transcriptional activation by 20-hydroxyecdysone (20E) in Drosophila provides an excellent model for studying tissue-specific responses to steroids. An increase the 20E concentration regulates degradation of larval and proliferation adult tissues during metamorphosis. To study 20E-dependent transcription, we used natural system controlling concentration—the E23 membrane transporter—which exports from cell. We artificially expressed suppress first wave 20E-inducible transcription at...
Abstract Telomeres ensure genome stability and the levels of telomeric RNA reflect integrity chromatin. The highly conserved RNA-binding protein Ars2 (Arsenite-resistance 2) plays an essential role in nuclear metabolism negatively regulates expression transcripts human cells Drosophila. We found that germline knockdown Drosophila does not affect small abundance but causes overexpression repeats transposable elements (TEs), accompanied by chromatin decompaction these regions. a transgene...
Enhancer elements determine the level of target gene transcription in a tissue-specific manner, providing for individual patterns expression different cells. Knowledge mechanisms controlling enhancer action is crucial understanding global regulation transcription. In particular, enhancers are often localized within transcribed regions genome. A number experiments suggest that can have both positive and negative effects on regulatory elements. this study, we performed direct tests effect...
Abstract The Polycomb group (PcG) proteins are fundamental epigenetic regulators that control the repressive state of target genes in multicellular organisms. One open questions is defining mechanisms PcG recruitment to chromatin. In Drosophila, crucial role thought belong DNA-binding associated with response elements (PREs). However, current data suggests not all PRE-binding factors have been identified. Here, we report identification transcription factor Crooked legs (Crol) as a novel...
The formation of individual gene expression patterns in different cell types is required during differentiation and development multicellular organisms. Polycomb group (PcG) proteins are key epigenetic regulators responsible for repression, dysregulation their activities leads to developmental abnormalities diseases. PcG were first identified Drosophila, which still remains the most convenient system studying PcG-dependent repression. In Drosophila genome, these bind DNA regions called...
PRC2 (Polycomb repressive complex 2) is an evolutionarily conserved protein required to maintain transcriptional repression. The core includes EZH2, SUZ12, and EED proteins methylates histone H3K27. known contribute carcinogenesis several small molecule inhibitors targeting have been developed. present study aimed identify the cancer types in which drugs could be beneficial. We queried genomic transcriptomic (cBioPortal, KMplot) database portals of clinical tumor samples evaluate...
Insulators are architectural elements implicated in the organization of higher-order chromatin structures and transcriptional regulation. However, it is still unknown how insulators contribute to Drosophila telomere maintenance. Although telomeric retrotransposons HeT-A TART occupy a common genomic niche, they regulated independently. believed provide reverse transcriptase activity, whereas transcripts serve as template for elongation. Here, we report that insulator complexes associate with...
Abstract Suppressor of Hairy-wing [Su(Hw)] is a DNA-binding architectural protein that participates in the organization insulators and repression promoters Drosophila . This contains acidic regions at both ends central cluster 12 zinc finger domains, some which are involved specific recognition binding site. One well-described vivo function Su(Hw) transcription neuronal genes oocytes. Here, we have found same C-terminal region (aa 720–892) required for insulation as well promoter repression....
Polycomb group (PcG) and Trithorax (TrxG) proteins are evolutionarily conserved factors responsible for the repression activation of transcription multiple genes in Drosophila mammals. Disruption PcG/TrxG expression is associated with many pathological conditions, including cancer, which makes them suitable targets diagnosis therapy medicine. In this review, we focus on major PcG TrxG complexes, mechanisms action, their recruitment to chromatin. We discuss alterations dysfunction a number...
Abstract Suppressor of Hairy-wing [Su(Hw)] is one the best characterized architectural proteins in Drosophila and recruits CP190 Mod(mdg4)-67.2 to chromatin, where they form a well-known insulator complex. Recently, HP1 partner protein 1 (HIPP1), homolog human co-repressor Chromodomain Y-Like (CDYL), was identified as new for Su(Hw). Here, we performed detailed analysis domains involved HIPP1 interactions with Su(Hw)-dependent complexes. found directly interact Su(Hw) C-terminal region (aa...
The identification of mechanisms that underlie the biology individual tumors is aimed at development personalized treatment strategies. Herein, we performed a comprehensive search genes (termed Supertargets) vital for particular tissue origin. In so doing, used DepMap database portal encompasses broad panel cell lines with knocked out by CRISPR/Cas9 technology. For each 27 tumor types, revealed top five whose deletion was lethal in case, indicating both known and unknown Supertargets. Most...