The establishment of the 3D genome structure during zygotic genome activation.

During zygotic genome activation (ZGA) and early development, hierarchical levels of chromatin structure undergo remarkable perturbations: changes in the nuclear-to-cytoplasmic ratio of various components; changes in chromatin accessibility; histone exchange; and the formation of 3D structures such as loops, topologically associated domains, and compartments. Here, we review the peculiarities, variability, and emergence of the chromatin structural features during ZGA in different organisms. Focusing on newly found structures called fountains, we describe the prerequisites for cohesin loading on DNA and possible mechanisms of genome organization in early development.

Memories of Ron Hancock.

This essay is in memoriam of Ronald Hancock (1933 - 2022).

Enhancer Function in the 3D Genome.

In this review, we consider various aspects of enhancer functioning in the context of the 3D genome. Particular attention is paid to the mechanisms of enhancer-promoter communication and the significance of the spatial juxtaposition of enhancers and promoters in 3D nuclear space. A model of an activator chromatin compartment is substantiated, which provides the possibility of transferring activating factors from an enhancer to a promoter without establishing direct contact between these elements.

Segregation of α- and β-Globin Gene Cluster in Vertebrate Evolution: Chance or Necessity?

The review is devoted to the patterns of evolution of α- and β-globin gene domains. A hypothesis is presented according to which segregation of the ancestral cluster of α/β-globin genes in Amniota occurred due to the performance by α-globins and β-globins of non-canonical functions not related to oxygen transport.

Co-Regulated Genes and Gene Clusters.

There are many co-regulated genes in eukaryotic cells. The coordinated activation or repression of such genes occurs at specific stages of differentiation, or under the influence of external stimuli. As a rule, co-regulated genes are dispersed in the genome.

Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals.

Due to their exceptional simplicity of organization, viruses rely on the resources, molecular mechanisms, macromolecular complexes, regulatory pathways, and functional compartments of the host cell for an effective infection process. The nucleolus plays an important role in the process of interaction between the virus and the infected cell. The interactions of viral proteins and nucleic acids with the nucleolus during the infection process are universal phenomena and have been described for almost all taxonomic groups.

Modification of Nuclear Compartments and the 3D Genome in the Course of a Viral Infection.

The review addresses the question of how the structural and functional compartmentalization of the cell nucleus and the 3D organization of the cellular genome are modified during the infection of cells with various viruses. Particular attention is paid to the role of the introduced changes in the implementation of the viral strategy to evade the antiviral defense systems and provide conditions for viral replication. The discussion focuses on viruses replicating in the cell nucleus.

Mechanisms mediating suppression of globin gene transcription in Danio rerio nonerythroid cells.

We studied the repression of adult and embryo-larval genes of the major globin gene locus in D. rerio fibroblasts. The results obtained suggest that at least some of the globin genes are repressed by Polycomb, similarly to human α-globin genes.

Nucleolus: A Central Hub for Nuclear Functions.

The nucleolus is the largest and most studied nuclear body, but its role in nuclear function is far from being comprehensively understood. Much work on the nucleolus has focused on its role in regulating RNA polymerase I (RNA Pol I) transcription and ribosome biogenesis; however, emerging evidence points to the nucleolus as an organizing hub for many nuclear functions, accomplished via the shuttling of proteins and nucleic acids between the nucleolus and nucleoplasm. Here, we discuss the cellular mechanisms affected by shuttling of nucleolar components, including the 3D organization of the genome, stress response, DNA repair and recombination, transcription regulation, telomere maintenance, and other essential cellular functions.

[Role of the Nucleolus in Rearrangements of the IGH Locus].

The review summarizes the results from a series of studies focusing on the role that the nucleolus plays in maturation of the IGH locus and the choice of its partner genes in leukemia-associated translocations. The role of nuclear compartmentalization and nuclear localization of translocated oncogenes in ectopic activation of their transcription is discussed.

Effect of Environmental Factors on Nuclear Organization and Transformation of Human B Lymphocytes.

Chromosomal translocations have long been known for their association with malignant transformation, particularly in hematopoietic disorders such as B-cell lymphomas. In addition to the physiological process of maturation, which creates double strand breaks in immunoglobulin gene loci, environmental factors including the Epstein-Barr and human immunodeficiency viruses, malaria-causing parasites (Plasmodium falciparum), and plant components (Euphorbia tirucalli latex) can trigger a reorganization of the nuclear architecture and DNA damage that together will facilitate the occurrence of deleterious chromosomal rearrangements.

Genetic and Epigenetic Mechanisms of β-Globin Gene Switching.

Vertebrates have multiple forms of hemoglobin that differ in the composition of their polypeptide chains. During ontogenesis, the composition of these subunits changes. Genes encoding different α- and β-polypeptide chains are located in two multigene clusters on different chromosomes.

The IGH locus relocalizes to a "recombination compartment" in the perinucleolar region of differentiating B-lymphocytes.

The immunoglobulin heavy chain (IGH) gene loci are subject to specific recombination events during B-cell differentiation including somatic hypermutation and class switch recombination which mark the end of immunoglobulin gene maturation in germinal centers of secondary lymph nodes. These two events rely on the activity of activation-induced cytidine deaminase (AID) which requires DNA double strand breaks be created, a potential danger to the cell. Applying 3D-fluorescence in situ hybridization coupled with immunofluorescence staining to a previously described experimental system recapitulating normal B-cell differentiation ex vivo, we have kinetically analyzed the radial positioning of the two IGH gene loci as well as their proximity with the nucleolus, heterochromatin and γH2AX foci.

HIV Tat induces a prolonged MYC relocalization next to IGH in circulating B-cells.

With combined antiretroviral therapy (cART), the risk for HIV-infected individuals to develop a non-Hodgkin lymphoma is diminished. However, the incidence of Burkitt lymphoma (BL) remains strikingly elevated. Most BL present a t(8;14) chromosomal translocation which must take place at a time of spatial proximity between the translocation partners.

Evolution of the Genome 3D Organization: Comparison of Fused and Segregated Globin Gene Clusters.

The genomes are folded in a complex three-dimensional (3D) structure. Some features of this organization are common for all eukaryotes, but little is known about its evolution. Here, we have studied the 3D organization and regulation of zebrafish globin gene domain and compared its organization and regulation with those of other vertebrate species.

Binding of Protein Factor CTCF within Chicken Genome Alpha-Globin Locus.

A systematic search for DNA fragments containing potential CTCF transcription factor binding sites in the chicken alpha-globin domain and its flanking regions was performed by means of the two-dimension electrophoretic mobility shift assay. For the alpha-globin domain fragments selected, the occupancy by the CTCF in erythroid and lymphoid chicken cells was tested by chromatin immunoprecipitation. Only one of 13 DNA fragments capable of CTCF binding in vitro was efficiently bound to this protein in vivo in erythroid cells, and somewhat less efficiently - in lymphoid cells.

Distinct Patterns of Colocalization of the CCND1 and CMYC Genes With Their Potential Translocation Partner IGH at Successive Stages of B-Cell Differentiation.

The immunoglobulin heavy chain (IGH) locus is submitted to intra-chromosomal DNA breakages and rearrangements during normal B cell differentiation that create a risk for illegitimate inter-chromosomal translocations leading to a variety of B-cell malignancies. In most Burkitt's and Mantle Cell lymphomas, specific chromosomal translocations juxtapose the IGH locus with a CMYC or Cyclin D1 (CCND1) gene, respectively. 3D-fluorescence in situ hybridization was performed on normal peripheral B lymphocytes induced to mature in vitro from a naive state to the stage where they undergo somatic hypermutation (SHM) and class switch recombination (CSR).

Characterization of the enhancer element of the Danio rerio minor globin gene locus.

In Danio rerio, the alpha- and beta-globin genes are present in two clusters: a major cluster located on chromosome 3 and a minor cluster located on chromosome 12. In contrast to the segregated alpha- and beta-globin gene domains of warm-blooded animals, in Danio rerio, each cluster contains both alpha- and beta-globin genes. Expression of globin genes present in the major cluster is controlled by an erythroid-specific enhancer similar to the major regulatory element of mammalian and avian alpha-globin gene domains.

[Detection of complementary transcripts in intergenic region of the chicken α-globin gene domain].

Using strand-specific reverse transcription followed by Real Time PCR analysis we have characterized the transcription profile of the segment of chicken α-globin gene domain harboring embryonic gene π, adult gene αD and spacer region separating these genes. It has been demonstrated that in erythroid cells of adult lineage the spacer region is transcribed in both directions. These results suggest a possibility that switching of α-globin genes expression is controlled by RNA-interference mechanism.

Nuclear localization of translocation partners in differentiating B-cells.

We studied the nuclear localization and relative position in the nuclear space of malignant translocation partner genes c-Myc, CCND1, and IGH locus in naive and differentiating B cells. We have shown that, during B-cell maturation, c-Myc and IGH loci become closer to each other. In differentiating lymphocytes, those alleles of c-Myc and IGH that are in close spatial proximity to each other are closer to the nucleolus.

[Joint locus of a/b-globin genes in Danio rerio is segregated into structural subdomains active at different stages of development].

In the domain model of eukaryotic genome organization, the functional unit of the genome, along with the relevant regulatory elements, is considered to be a gene or a gene family. In hot-blooded vertebrate animals, the domains of a- and b-globin genes are positioned at different chromosomes and are organized and regulated in different fashion. In cold-blooded animals, in particular in tropical fish Danio rerio, a- and b globin genes are located in a common gene cluster.

Evolution of α- and β-globin genes and their regulatory systems in light of the hypothesis of domain organization of the genome.

The α- and β-globin gene domains are a traditional model for study of the domain organization of the eucaryotic genome because these genes encode hemoglobin, a physiologically important protein. The α-globin and β-globin gene domains are organized in completely different ways, while the expression of globin genes is tightly coordinated, which makes it extremely interesting to study the origin of these genes and the evolution of their regulatory systems. In this review, the organization of the α- and β-globin gene domains and their genomic environment in different taxonomic groups are comparatively analyzed.

Nuclear matrix and structural and functional compartmentalization of the eucaryotic cell nucleus.

Becoming popular at the end of the 20th century, the concept of the nuclear matrix implies the existence of a nuclear skeleton that organizes functional elements in the cell nucleus. This review presents a critical analysis of the results obtained in the study of nuclear matrix in the light of current views on the organization of the cell nucleus. Numerous studies of nuclear matrix have failed to provide evidence of the existence of such a structure.

The clustering of CpG islands may constitute an important determinant of the 3D organization of interphase chromosomes.

We used the 4C-Seq technique to characterize the genome-wide patterns of spatial contacts of several CpG islands located on chromosome 14 in cultured chicken lymphoid and erythroid cells. We observed a clear tendency for the spatial clustering of CpG islands present on the same and different chromosomes, regardless of the presence or absence of promoters within these CpG islands. Accordingly, we observed preferential spatial contacts between Sp1 binding motifs and other GC-rich genomic elements, including the DNA sequence motifs capable of forming G-quadruplexes.