Nucleolus and rRNA Gene Chromatin in Early Embryo Development

Abstract

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...

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

“…Classical nucleoli in growing oocytes transform to NPB in fully grown oocyte and disappear during meiotic maturation. Upon fertilization, NPB reappears in both pronuclei of zygotes, gradually disappears, and eventually converts to typical nucleoli with tripartite structure . Because NOP2 is restrictedly localized within the nucleolus and involved in ribosome assembly in yeast, we first examined whether the nucleolar structure was affected upon NOP2 depletion.…”

“…It is well documented that the fibrillar center (NPB) plays no role in transcription and active transcription of rDNA occurs in FCs of the nucleolus. 1,33 We found that the ratio of NPB area to the nucleolar area ( Figure 5A,C) was increased and the number of FCs declined ( Figure 5A,D), suggesting a compromised rDNA transcription activity in KD embryos. Altogether, these results showed that NOP2 is a nucleolar protein critically important for the remodeling of nucleolar structure during preimplantation development.…”

“…There is a high electron density in the fibrillar sphere, consisting of a network of densely and uniformly packed filaments as reported before. 1,28,33 However, the ratio of nucleolar to nuclear area was significantly reduced in KD embryos, suggesting the nucleolar maturation is inhibited ( Figure 5A,B). It is well documented that the fibrillar center (NPB) plays no role in transcription and active transcription of rDNA occurs in FCs of the nucleolus.…”

“…Nucleolar structure is reprogrammed dramatically during oocyte-to-embryo transition. 1,33 Classical nucleoli in growing oocytes transform to NPB in fully grown oocyte and disappear during meiotic maturation. Upon fertilization, NPB reappears in both pronuclei of zygotes, gradually disappears, and eventually converts to typical nucleoli with tripartite structure.…”

“…1,2 However, a NPB is composed of a compact fibrillar compartment with unknown composition. 1,3 Maternal nucleoli are required for proper ZGA, whereas fertilized, enucleolated oocytes are not capable of developing beyond the four-cell stage in mice. 4 Although the primary role of the nucleolus is the production of ribosome RNA and ribosome assembly, growing evidence has revealed its importance in a variety of cellular processes, including regulation of cell cycle progression and apoptosis.…”