A5044157162- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Genetic Associations and Epidemiology
- Genetic Syndromes and Imprinting
- Plant Virus Research Studies
- Gene Regulatory Network Analysis
- RNA modifications and cancer
- DNA Repair Mechanisms
- Plant Molecular Biology Research
- Hemoglobinopathies and Related Disorders
- Bioinformatics and Genomic Networks
- Protein Structure and Dynamics
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Genomics and Phylogenetic Studies
- Cancer-related molecular mechanisms research
- Identity, Memory, and Therapy
- Genetic Mapping and Diversity in Plants and Animals
- Chromosomal and Genetic Variations
- Gut microbiota and health
- DNA and Nucleic Acid Chemistry
- Nuclear Structure and Function
- ECG Monitoring and Analysis
Institute of Gene Biology
2013-2024
Technion – Israel Institute of Technology
2023-2024
Lomonosov Moscow State University
2013-2023
Mental Health Research Center of Russian Academy of Medical Sciences
2018-2021
Russian Academy of Sciences
2021
Vavilov Institute of General Genetics
2014
Abstract Liquid–liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes within cell nucleus. However, role played by LLPS in chromatin folding living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) Hi-C techniques, we studied effects 1,6-hexanediol (1,6-HD)-mediated disruption/modulation on higher-order organization cells. We found that 1,6-HD treatment caused enlargement nucleosome clutches their...
Abstract Recently we characterized a class of anti-cancer agents (curaxins) that disturbs DNA/histone interactions within nucleosomes. Here, using combination genomic and in vitro approaches, demonstrate curaxins strongly affect spatial genome organization compromise enhancer-promoter communication, which is necessary for the expression several oncogenes, including MYC . We further show selectively inhibit enhancer-regulated transcription chromatinized templates cell-free conditions. Genomic...
Abstract Non-coding RNAs (ncRNAs) participate in various biological processes, including regulating transcription and sustaining genome 3D organization. Here, we present a method termed Red-C that exploits proximity ligation to identify contacts with the for all RNA molecules nucleus. Using Red-C, uncovered RNA–DNA interactome of human K562 cells identified hundreds ncRNAs enriched active or repressed chromatin, previously undescribed RNAs. Analysis also allowed us trace kinetics messenger...
Chromosome conformation capture (3C) and derivative experimental procedures are used to estimate the spatial proximity between different genomic elements, thus providing information about 3D organization of domains whole genomes within nucleus. All C-methods based on ligation-the preferential ligation joined DNA fragments obtained upon restriction enzyme digestion in vivo cross-linked chromatin. Here, using mouse beta-globin genes erythroid cells as a model, we estimated actual frequencies...
In homeotherms, the alpha-globin gene clusters are located within permanently open genome regions enriched in housekeeping genes. Terminal erythroid differentiation results dramatic upregulation of genes making their expression comparable to rRNA transcriptional output. Little is known about influence erythroid-specific transcription outburst on adjacent, widely expressed and large-scale chromatin organization. Here, we have analyzed total output, overall contact profile, CTCF binding 2.7 Mb...
The enhancer-promoter looping model, in which enhancers activate their target genes via physical contact, has long dominated the field of gene regulation. However, ubiquity this model been questioned due to evidence alternative mechanisms and lack its systematic validation, primarily owing absence suitable experimental techniques. In study, we present a new MNase-based proximity ligation method called MChIP-C, allowing for measurement protein-mediated chromatin interactions at...
Methylation of DNA is associated with a variety biological processes. With whole-genome studies methylation, it became possible to determine set genomic sites where methylation specific phenotype. A method needed that allows detailed follow-up the sites, including taking into account genetic information. Bisulfite PCR natural choice for this kind task, but multiplexing one most important problems impeding its implementation. To address we took advantage recently published based on Pacbio...
There is a decrease in the expression of reelin gene (RELN) brain schizophrenia patients, which can underlie observed cognitive abnormalities. It suggested that this caused by hypermethylation RELN promoter. The aim study was to investigate methylation promoter peripheral blood patients and its association with their deficits. A modified SMRT-BS (single-molecule real-time bisulfite sequencing) used. We determined rate 170 CpG sites within 1465 bp DNA region containing entire island 51 52...
Cohesin is a key organizer of chromatin folding in eukaryotic cells. The two main activities this ring-shaped protein complex are the maintenance sister chromatid cohesion and establishment long-range DNA-DNA interactions through process loop extrusion. Although basic principles both extrusion have been described, we still do not understand several crucial mechanistic details. One such unresolved issues question whether cohesin ring topologically embraces DNA string(s) during Here, show that...
Abstract Large-scale epigenomic projects have mapped hundreds of thousands potential regulatory sites in the human genome, but only a small proportion these elements are proximal to transcription start sites. It is believed that majority sequences remote promoter-activating genomic scattered within several kilobases from their cognate promoters and referred as enhancers. still unclear what principles, aside relative closeness linear determine which promoter(s) controlled by given enhancer;...
Abstract The enhancer-promoter looping model, in which enhancers activate their target genes via physical contact, has long dominated the field of gene regulation. However, ubiquity this model been questioned due to evidence alternative mechanisms and lack its systematic validation, primarily owing absence suitable experimental techniques. In study, we present a new MNase-based proximity ligation method called MChIP-C, allowing for measurement protein-mediated chromatin interactions at...
The enhancer-promoter looping model, in which enhancers activate their target genes via physical contact, has long dominated the field of gene regulation. However, ubiquity this model been questioned due to evidence alternative mechanisms and lack its systematic validation, primarily owing absence suitable experimental techniques. In study, we present a new MNase-based proximity ligation method called MChIP-C, allowing for measurement protein-mediated chromatin interactions at...
Abstract Liquid-liquid phase separation (LLPS) contributes to the spatial and functional segregation of molecular processes. However, role played by LLPS in chromatin folding living cells remains unclear. Here, using stochastic optical reconstruction microscopy (STORM) Hi-C techniques, we studied effects 1,6-hexanediol (1,6-HD)-mediated modulation on higher-order organization cells. We found that 1,6-HD treatment caused enlargement nucleosome nanodomains their more uniform distribution...
The extremely high concentration of macromolecules in a eukaryotic cell nucleus indicates that the nucleoplasm is crowded macromolecular solution which large objects tend to gather together due crowding forces. It has been shown experimentally forces support integrity various nuclear compartments. However, little known about their role control chromatin dynamics vivo. Here, we addressed possible spatial organization genome. Using mouse β-globin domain as model, demonstrated juxtaposition...
Abstract Chromatin loops represent one of the major levels hierarchical folding genome. Although situation is evolving, current methods have various difficulties with accurate mapping even in mammalian Hi-C data, and most them fail to identify chromatin animal species substantially different genome architecture. This paper presents loop significant contact annotation (LASCA) pipeline, which uses Weibull distribution-based modeling effectively enhancer–promoter interactions data from...
The eukaryotic nucleus harbors genomic DNA, which is tens of thousands times greater in linear size than the nuclear diameter.Its high condensation due to DNA packaging chromatin, and wrapping around nucleosomal globules a key step process.A histone octamer, forms globule, interacts with via electrostatic contacts.DNA-histone interactions are rather tight prevent from being accessed by various enzymes transcription factors.At same time, nucleosomes do not other processes related genetic...
Abstract Interrogating DNA methylation within schizophrenia risk loci holds promise to identify mechanisms by which genes influence the disease. Based on hypothesis that allele specific (ASM) of a single CpG, or perhaps CpH, might mediate mark effects genetic variants disease and phenotypes, we explored haplotype levels individual cytosines genomic region harbouring BAG5 , APOPT1 KLC1 in peripheral blood patients healthy controls. Three fragments located promoter, intronic intergenic areas...