Yuri M Moshkin

Yuri M Moshkin
Institute of Cytology and Genetics

PhD

About

69
Publications
8,213
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3,332
Citations
Additional affiliations
January 2005 - August 2015
Erasmus MC
Position
  • PostDoc Position

Publications

Publications (69)
Article
Nanoparticles are capable of penetrating cells, but little is known about the way they interact with intracellular proteome. Here we showed that inorganic nanoparticles associate with low-complexity, intrinsically disordered proteins from HeLa cytosolic protein extracts in non-denaturing in vitro nanoparticle pull-down assays. Intrinsic protein dis...
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Nucleosomal DNA is thought to be generally inaccessible to DNA-binding factors, such as micrococcal nuclease (MNase). Here, we digest Drosophila chro-matin with high and low concentrations of MNase to reveal two distinct nucleosome types: MNase-sensitive and MNase-resistant. MNase-resistant nu-cleosomes assemble on sequences depleted of A/T and enr...
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Most of eukaryotic DNA is embedded into nucleosome arrays formed by DNA wrapped around a core histone octamer. Nucleosome is a fundamental repeating unit of chromatin guarding access to the genetic information. Here, I will discuss two facets of nucleosome in eukaryotic gene control. On the one hand, nucleosome acts as a regulatory unit, which cont...
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Author Summary Eukaryotic DNA is assembled into a nucleo-protein structure called chromatin. Nucleosomes are the basic building blocks of chromatin, comprising 147 bp of DNA tightly wrapped around a histone protein core. Histone chaperones mediate nucleosome assembly by preventing non-productive aggregation of histones with DNA. Here, we describe a...
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Histone chaperones are involved in a variety of chromatin transactions. By a proteomics survey, we identified the interaction networks of histone chaperones ASF1, CAF1, HIRA, and NAP1. Here, we analyzed the cooperation of H3/H4 chaperone ASF1 and H2A/H2B chaperone NAP1 with two closely related silencing complexes: LAF and RLAF. NAP1 binds RPD3 and...
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The latest vaccination campaign has actualized the potential impact of antigenic stimuli on reproductive functions. To address this, we mimicked vaccination’s effects by administering keyhole limpet hemocyanin (KLH ) to CD1 male mice and used their sperm for in vitro fertilization (IVF). Two-cell embryos after IVF with spermatozoa from control (C)...
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ATP-dependent chromatin remodelers control the accessibility of genomic DNA through nucleosome mobilization. However, the dynamics of genome exploration by remodelers, and the role of ATP hydrolysis in this process remain unclear. We used live-cell imaging of Drosophila polytene nuclei to monitor Brahma (BRM) remodeler interactions with its chromos...
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Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is challenging. This stems from the heterogeneous response of individuals to disease and is reflected in the inter-individual variability of gene expression responses that obscures differential gene expression analysis. Here, we developed an alternative app...
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Exposure to nanomaterials is considered as one of the risk factors for neurodegenerative pathology. In vitro inorganic nanoparticles (NPs) absorb intrinsically disordered proteins, many of which are the constituents of stress-granules (SGs). SGs normally form in response to cellular stress and, here, we addressed whether selected inorganic NPs coul...
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Assisted reproductive technologies (ART) increasingly occupy the study of human reproduction. In addition, in developed countries they contribute to breeding of more than 50 % of cattle. In the management of collections of genetic lines of laboratory animals, these technologies are obligatory components of cryopreservation and rederivation. ART pro...
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We analyzed the whole-genome experimental maps of nucleosomes in Drosophila melanogaster and classified genes by the expression level in S2 cells (RPKM value, reads per kilobase million) as well as the number of tissues in which a gene was expressed (breadth of expression, BoE). Chromatin in 5′-regions of genes we classified on four states accordin...
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Finding novel biomarkers for human pathologies and predicting clinical outcomes for patients is rather challenging. This stems from the heterogenous response of individuals to disease which is also reflected in the inter-individual variability of gene expression responses. This in turn obscures differential gene expression analysis (DGE). In the mi...
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The life-history theory suggests that parental experience of the environment is passed to offspring, which allows them to adapt to prevailing conditions. This idea is supported from the mother’s side, but to a much less extent from the father’s side. Here, we investigated the effect of immunising fathers on pre- and neonatal development and on immu...
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Transcriptome sequencing is a powerful technique to study molecular changes that underlie the differences in physiological conditions and disease progression. A typical question that is posed in such studies is finding genes with significant changes between sample groups. In this respect expression variability is regarded as a nuisance factor that...
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There is a canonical life-history trade-off between quantity and quality of offspring, but molecular determinants for this are unknown. Here, we show that knockout of tumor necrosis factor (TNF-KO) in mice switched a relation between the number and size of developing embryos from expectedly negative to unexpectedly positive. Depletion of TNFα imbal...
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Study question: Does the genotype of the surrogate mother modulate the body composition and immunity of her offspring? Summary answer: C57BL/6J (B6) progenies carried by immunodeficient NOD SCID (NS) mothers had increased adaptive, but decreased innate, immune responsiveness in comparison with the same genotype offspring carried by immunocompete...
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Long-lived systems are expected to be stable, i. e. resistant to either external influences, or internal failures. Robustness of biological systems can be defined as a reciprocal value to their phenotypic plasticity expressed through a coefficient of variation (C.V.) for positively distributed phenotypic traits. Considering lifespan as phenotype, w...
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The ability to deliver particulated xenobiotics and therapeutic drugs directly from the nasal cavity to the central nervous system, bypassing the hemato-encephalic barrier, determines a high importance of investigation of factors influencing this process. It was shown that the bioavailability of solid particles is influenced by their size and surfa...
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The silent information regulator 1 (Sirt1) has previously been shown to have negative effects on the Notch pathway in several contexts. We bring evidence that Sirt1 has a positive effect on Notch activation in Drosophila, in the context of sensory organ precursor specification and during wing development. The phenotype of Sirt1 mutant resembles wea...
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During spermatogenesis, the paternal genome is repackaged into a non-nucleosomal, highly compacted chromatin structure. Bioinformatic analysis revealed that Drosophila sperm chromatin proteins are characterized by a motif related to the highmobility group (HMG) box, which we termed malespecific transcript (MST)-HMG box. MST77F is a MST-HMG-box prot...
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The modification of pre- and postnatal development conferred by immunogenic stimulation of mothers provides a population-level adaptation mechanism for non-genetic transfer of maternal experiences to progeny. However little is known about the transmission of paternal immune experiences to offspring. Here, we show that immune priming of males 3-9 da...
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Increasing amounts of data support a role for guanine quadruplex (G4) DNA and RNA structures in various cellular processes. We stained different organisms with monoclonal antibody 1H6 specific for G4 DNA. Strikingly, immuno-electron microscopy showed exquisite specificity for heterochromatin. Polytene chromosomes from Drosophila salivary glands sho...
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Inhalation of air-dispersed sub-micrometre and nano-sized particles presents a risk factor for animal and human health. Here, we show that nasal aerodynamics plays a pivotal role in the protection of the subterranean mole vole Ellobius talpinus from an increased exposure to nano-aerosols. Quantitative simulation of particle flow has shown that thei...
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One of the most dramatic forms of chromatin reorganization occurs during spermatogenesis, when the paternal genome is repackaged from a nucleosomal to a protamine-based structure. We assessed the role of the canonical histone chaperone CAF1 in Drosophila spermatogenesis. In this process, CAF1 does not behave as a complex, but its subunits display d...
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Cells need to coordinate gene expression and metabolic state. Inosine monophosphate dehydrogenase (IMPDH) controls the guanine nucleotide pool and, thereby, cell proliferation. We found that Drosophila IMPDH is also a DNA-binding transcriptional repressor. IMPDH attenuates expression of histone genes and E2f, a key driver of cell proliferation. Nuc...
Data
The BAF250a, but not BAF250b-containing BAF complex, is specifically required for maintenance of repression of latent HIV. (A) J-Lat A2 cells latently infected with LTR-Tat-IRES GFP virus were nucleofected with either control siRNA or siRNAs targeting BAF250a, BAF250b, and BRG-1 as indicated. GFP mRNA expression was determined by RT-PCR at the time...
Data
BAF180-facilitated Tat activation of the LTR is dependent on Tat residues K50,51. (A) CMV-driven luciferase activity is not affected by the depletion of either BAF180 or BAF250a. Jurkat cells were nucleofected with siRNAs against BAF180, BAF250, or with a control siRNA pool. Forty-eight hours after siRNA treatment, cells were transfected with a CMV...
Data
Analysis of chromatin structure and direct binding of distinct SWI/SNF complexes to the HIV promoter before and after PMA stimulation in J-Lat A2. (A) PMA stimulation causes increase in DNA accessibility over the LTR nuc-1. FAIRE results are presented as fold change respective to unstimulated value for each primer pair. (B) PMA stimulation is accom...
Data
ATP depletion results in nuc-1 remodeling and HIV promoter activation. (A) Schematic representation of the restriction sites and probe used to analyze the remodeling of nuc-1. Nuclei isolated from cells treated either with PMA or sodium azide (NaN3) were digested in vitro with AflII to probe for accessibility of the DNA encompassing nuc-1. Genomic...
Data
BAF promotes the establishment of latent HIV infections in SupT1 cells. (A) Top panel: schematic representation of protocol for comparison of productive and latent infections in SupT1 cells containing or depleted of remodeling complex subunits. SupT1 cells were first nucleofected with control siRNA or siRNA targeting individual SWI/SNF subunits as...
Data
BAF and CHD3 do not synergize in promoting the establishment of latent HIV infections. Jurkat cells (A-C) or SupT1 cells (D-F) were first nucleofected with control siRNA or siRNA targeting BAF250, BRG1, CHD3, BAF250 together with CHD3, or BRG1 together with CHD3. After 48 hours, cells were infected with retroviral particles containing the vector LT...
Data
Stability of SWI/SNF complex component protein levels after siRNA depletion of individual subunits. Jurkat cells containing an integrated LTR-GFP virus (clone D) were transfected with either control siRNA or siRNAs targeting various SWI/SNF complex subunits as indicated. Western blot analysis shows expression of SWI/SNF complex subunits in presence...
Data
BAF positions nuc-1 of HIV LTR. (A) Location of strictly positioned nucleosomes correlate negatively with the predicted histone binding affinity score (nucleosome score) of the DNA sequence encompassing the HIV LTR. Similarity of the predicted nucleosome affinity for HIV nucleotide sequence 1–1800 determined using the algorithm described in (Xi et...
Data
Primer pairs used to analyze ChIP, FAIRE, and MNase experiments by qPCR. (PDF)
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The nucleosome is the fundamental repeating unit of eukaryotic chromatin. Here, we assessed the interplay between DNA sequence and ATP-dependent chromatin-remodeling factors (remodelers) in the nucleosomal organization of a eukaryotic genome. We compared the genome-wide distribution of Drosophila NURD, (P)BAP, INO80, and ISWI, representing the four...
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Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradication in treated patients. Several reports have implicated the involvement of SWI/SNF chromatin remodeling complexes in restricting early steps in HIV infection, in coupling the processes of integration and remodeling, and in promoter/LTR transcription ac...
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ATP-dependent chromatin-remodeling complexes (remodelers) are essential regulators of chromatin structure and gene transcription. How remodelers can act in a gene-selective manner has remained enigmatic. A yeast two-hybrid screen for proteins binding the Drosophila transcription factor Tramtrack69 (TTK69) identified MEP1. Proteomic characterization...
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Histone chaperones are at the hub of a diverse interaction networks integrating a plethora of chromatin modifying activities. Histone H3/H4 chaperone ASF1 is a target for cell-cycle regulated Tousled-like kinases (TLKs) and both proteins cooperate during chromatin replication. However, the precise role of post-translational modification of ASF1 rem...
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Drosophila GMP synthetase binds ubiquitin-specific protease 7 (USP7) and is required for its ability to deubiquitylate histone H2B. Previously, we showed that the GMPS/USP7 complex cooperates with the Polycomb silencing system through removal of the active ubiquitin mark from histone H2B (H2Bub). Here, we explored the interplay between GMPS and USP...
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An important hallmark in embryonic development is characterized by the maternal-to-zygotic transition (MZT) where zygotic transcription is activated by a maternally controlled environment. Post-transcriptional and translational regulation is critical for this transition and has been investigated in considerable detail at the gene level. We used a p...
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Transcription regulation involves enzyme-mediated changes in chromatin structure. Here, we describe a novel mode of histone crosstalk during gene silencing, in which histone H2A monoubiquitylation is coupled to the removal of histone H3 Lys 36 dimethylation (H3K36me2). This pathway was uncovered through the identification of dRING-associated factor...
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SWI/SNF ATP-dependent chromatin remodeling complexes (remodelers) perform critical functions in eukaryotic gene expression control. BAP and PBAP are the fly representatives of the two evolutionarily conserved major subclasses of SWI/SNF remodelers. Both complexes share seven core subunits, including the Brahma ATPase, but differ in a few signature...
Article
The histone chaperone Asf1 assists in chromatin assembly and remodeling during replication, transcription activation, and gene silencing. However, it has been unclear to what extent Asf1 could be targeted to specific loci via interactions with sequence-specific DNA-binding proteins. Here, we show that Asf1 contributes to the repression of Notch tar...
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Drosophila BAP and PBAP represent two evolutionarily conserved subclasses of SWI/SNF chromatin remodelers. The two complexes share the same core subunits, including the BRM ATPase, but differ in a few signature subunits: OSA defines BAP, whereas Polybromo (PB) and BAP170 specify PBAP. Here, we present a comprehensive structure-function analysis of...
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The spatial organization of DNA in the cell nucleus is an emerging key contributor to genomic function. We developed 4C technology (chromosome conformation capture (3C)-on-chip), which allows for an unbiased genome-wide search for DNA loci that contact a given locus in the nuclear space. We demonstrate here that active and inactive genes are engage...
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A cis-regulatory region of nearly 300 kb controls the expression of the three bithorax complex (BX-C) homeotic genes: Ubx, abd-A and Abd-B. Interspersed between the numerous enhancers and silencers within the complex are elements called domain boundaries. Recently, many pieces of evidence have suggested that boundaries function to create autonomous...
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The packaging of eukaryotic genomic DNA into chromatin is modulated through a range of posttranslational histone modifications. Among these, the role of histone ubiquitylation remains poorly understood. Here, we show that the essential Drosophila ubiquitin-specific protease 7 (USP7) contributes to epigenetic silencing of homeotic genes by Polycomb...
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Tousled-like kinases (TLKs) constitute a family of serine/threonine kinases conserved in plants and animals that act in a cell cycle-dependent manner. In mammals, their activity peaks during S phase, when they phosphorylate the antisilencing function protein 1 (ASF1), a histone chaperone involved in replication-dependent chromatin assembly. Here, w...
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De novo chromatin assembly into regularly spaced nucleosomal arrays is essential for eukaryotic genome maintenance and inheritance. The Anti-Silencing Function 1 protein (ASF1) has been shown to be a histone chaperone, participating in DNA-replication-coupled nucleosome assembly. We show that mutations in the Drosophila asf1 gene derepress silencin...
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In the Suppressor of Underreplication( SuUR) mutant strain of Drosophila melanogaster, the heterochromatin of polytene chromosomes is not underreplicated and, as a consequence, a number of beta-heterochromatic regions acquire a banded structure. The chromocenter does not form in these polytene chromosomes, and heterochromatic regions, normally part...