Disruption of the UBF gene induces aberrant somatic nucleolar bodies and disrupts embryo nucleolar precursor bodies

Hamdane, Nourdine; Tremblay, Michel G.; Dillinger, Stefan; Stefanovsky, Victor Y.; Németh, Attila; Moss, Tom

doi:10.1016/j.gene.2016.09.013

Cited by 16 publications

(23 citation statements)

References 29 publications

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“…These caps corresponded to those observed in SN oocytes and in interphase cells treated with inhibitors of Pol I transcription. Similar structures were also observed in UBF-null embryos, where NPBs were also either no longer apparent or strongly perturbed [48].…”

Section: Box 1 Preimplantation Developmental Stagessupporting

confidence: 73%

“…Interestingly, zygotes generated from enucleolated oocytes showed alterations in higher chromatin organization, as evidenced by the appearance of heterochromatin in the form of scattered dots [69]. Alterations in heterochromatin detected through DAPI staining were also reported in UBF-null embryos, which lack NPBs [48]. Studies indicated an important role of nucleoplasmin 2 (NPM2) in the function of NLB and NPB linked to genome organization during early embryo development [70].…”

Section: Box 1 Preimplantation Developmental Stagesmentioning

confidence: 96%

“…development. Embryos lacking RNA polymerase 1-2 (RPO1-2) or UBF arrest development before the morula stage [48,49]. Furthermore, pharmacological inhibition of rRNA gene transcription using CX-5461 [50] induced developmental delay and arrest at the four-cell stage [51].…”

Section: Box 1 Preimplantation Developmental Stagesmentioning

confidence: 99%

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Nucleolus and rRNA Gene Chromatin in Early Embryo Development

Kresoja‐Rakic

Santoro

2019

Trends in Genetics

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The nucleolus is the largest substructure in the nucleus and forms around the nucleolar organizer regions (NORs), which comprise hundreds of rRNA genes. Recent evidence highlights further functions of the nucleolus that go beyond ribosome biogenesis. Data indicate that the nucleolus acts as a compartment for the location and regulation of repressive genomic domains and, together with the nuclear lamina, represents the hub for the organization of the inactive heterochromatin. In this review, we discuss recent findings that have revealed how nucleolar structure and rRNA gene chromatin states are regulated during early mammalian development and their contribution to the higher-order spatial organization of the genome. The Multifunctional Nucleolus: From Ribosome Producer to Organizer of Genome Architecture The nucleolus (see Glossary) is the largest subnuclear compartment of the cell and forms around regions of chromosomes containing stretches of tandem repetitive rRNA genes, known as nucleolar organizer regions (NORs). The nucleolus is responsible for the production of ribosomes, a highly regulated process that is essential for growth and development. Ribosome biogenesis is initiated in the nucleolus by RNA polymerase I (Pol I), which, together with a dedicated set of basal transcription factors, such as TIF1A, the TBP-TAFI complex SL1, and the DNA architectural upstream binding factor (UBF) [1,2], transcribes hundreds of rRNA genes to generate 45S/47S pre-rRNA in mammalian cells (Figure 1A). This rRNA precursor is chemically modified and processed to form 28S, 18S, and 5.8S rRNAs, which are then assembled with ribosomal proteins and 5S rRNA and exported from the nucleus to give rise to active ribosomes in the cytoplasm [3]. Increasing evidence suggests that the function of the nucleolus and rRNA genes goes beyond ribosome biogenesis. One aspect that has received significant interest over the past decade is the link between the nucleolus and rRNA genes with the organization of genome architecture. Clustering of heterochromatin at nucleoli is a phenomenon that occurs in all cells. Furthermore, regions located close to the nucleolus (nucleolar-associated domains, NADs) have low gene densities, low transcriptional levels, and repressive histone modifications [4-8]. Since similar heterochromatic and repressive regions are also located to the nuclear lamina, the nucleolus, together with the nuclear lamina, can be considered the hub for the organization of the inactive chromatin in the cell [8-10]. In this review, we address the role of the nucleolus as a subnuclear compartment for the organization of heterochromatin. We discuss recent findings that have revealed how nucleolar structure and rRNA gene chromatin states are regulated during gametogenesis and early mammalian development, and their contribution in the higher-order spatial organization of the genome. Nucleolus and rRNA Genes in Somatic Cells In somatic cells, the nucleolus is a membraneless compartment with a peculiar tripartite architecture: the fibrillar cen...

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Section: Box 1 Preimplantation Developmental Stagessupporting

confidence: 73%

Section: Box 1 Preimplantation Developmental Stagesmentioning

confidence: 96%

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Nucleolus and rRNA Gene Chromatin in Early Embryo Development

Kresoja‐Rakic

Santoro

2019

Trends in Genetics

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“…40 Deletion of RNA polymerase 1-2 (RPO1-2) or UBF results in developmental arrest prior to the morula stage. 29,31 In the present study, we show NOP2 is first detected in late two-cell stage and its depletion results in a significant reduction of rRNA expression, regardless of the precursor and mature rRNAs. Also, TEM analyses revealed a reduction in the number of FCs, where rRNA gene transcription typically occurs.…”

Section: Discussionsupporting

confidence: 58%

The nucleolar protein NOP2 is required for nucleolar maturation and ribosome biogenesis during preimplantation development in mammals

Wang

et al. 2019

FASEB j.

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The maternal nucleolus plays an indispensable role in zygotic genome activation (ZGA) and early embryonic development in mice. During oocyte-to-embryo transition, the nucleolus is subject to substantial transformation. Despite the primary role of the nucleolus is ribosome biogenesis, accumulating evidence has uncovered its functions in various other cell processes. However, the regulation of nucleolar maturation and ribosome biogenesis and the molecules involved remain unclear during early embryonic development. In this study, we observed that nucleolar protein 2 (NOP2) is restrictedly localized within the nucleolus, first detected in the late two-cell embryos, and increases to a peak level at the eight-cell stage in mice. RNAi-mediated NOP2 depletion leads to a developmental arrest during the morula-to-blastocyst transition. RNA-seq analyses reveal that 208 genes are differentially expressed, including multiple lineage-specific genes and several genes encoding ribosome proteins.Indeed, we observe a failure of the first lineage specification with reduced TEA domain transcription factor 4(TEAD4) (trophectoderm-specific), tir na nog (NANOG), and kruppel-like factor 4 (KLF4) (inner cell mass-specific). Importantly, by Transm ission Electron Microscopy (TEM), we noted a decrease in the ratio of the nucleolus size and an increase in the ratio of the size of the nucleolus precursor body, suggesting the nucleolar maturation is disrupted. Moreover, both qPCR and Fluorescence I n Situ Hybridization (FISH) data showcase a significant decrease in the abundance of ribosome RNAs. Similarly, NOP2 depletion causes reduced developmental potential and decreased rRNA level in bovine early embryos, suggesting a functional 2716 |

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“…What factors are involved in formation of a FC phase? Clearly, UBF is essential, as without it pseudo‐NORs fail to form . Furthermore, UBF‐depleted endogenous NORs are both silent and not associated with nucleoli .…”

Section: Integrating Human Nor Genomic Architecture With the Liquid‐lmentioning

confidence: 99%

Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli

2017

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Nucleoli are the sites of ribosome biogenesis and the largest membraneless subnuclear structures. They are intimately linked with growth and proliferation control and function as sensors of cellular stress. Nucleoli form around arrays of ribosomal gene (rDNA) repeats also called nucleolar organizer regions (NORs). In humans, NORs are located on the short arms of all five human acrocentric chromosomes. Multiple NORs contribute to the formation of large heterochromatin-surrounded nucleoli observed in most human cells. Here we will review recent findings about their genomic architecture. The dynamic nature of nucleoli began to be appreciated with the advent of photodynamic experiments using fluorescent protein fusions. We review more recent data on nucleoli in Xenopus germinal vesicles (GVs) which has revealed a liquid droplet-like behavior that facilitates nucleolar fusion. Further analysis in both Xenopus GVs and Drosophila embryos indicates that the internal organization of nucleoli is generated by a combination of liquid-liquid phase separation and active processes involving rDNA. We will attempt to integrate these recent findings with the genomic architecture of human NORs to advance our understanding of how nucleoli form and respond to stress in human cells.

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Disruption of the UBF gene induces aberrant somatic nucleolar bodies and disrupts embryo nucleolar precursor bodies

Cited by 16 publications

References 29 publications

Nucleolus and rRNA Gene Chromatin in Early Embryo Development

Nucleolus and rRNA Gene Chromatin in Early Embryo Development

The nucleolar protein NOP2 is required for nucleolar maturation and ribosome biogenesis during preimplantation development in mammals

Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli

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