Nucleolar tethering mediates pairing between the<i>IgH</i>and<i>Myc</i>loci

Strongin, Daniel E.; Groudine, Mark; Politz, Joan C. Ritland

doi:10.4161/nucl.36233

Cited by 17 publications

(15 citation statements)

References 53 publications

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“…C57 mice have NORs on both chromosome 12 and chromosome 15, while CBA/CaJ (CBA) mice have a NOR on chromosome 15 but not on chromosome 12, and 129P3/J (129P3) mice have a NOR on chromosome 12 but not on chromosome 15 (Strongin et al 2014). It is possible that this variation between mouse strains may simply reflect differences in rDNA content of NORs between mouse strains rather than the absence or presence of NORs as such.…”

Section: Rdna Arrays and Norsmentioning

confidence: 87%

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

2016

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Nucleoli form around tandem arrays of a ribosomal gene repeat, termed nucleolar organizer regions (NORs). During metaphase, active NORs adopt a characteristic undercondensed morphology. Recent evidence indicates that the HMG-box-containing DNA-binding protein UBF (upstream binding factor) is directly responsible for this morphology and provides a mitotic bookmark to ensure rapid nucleolar formation beginning in telophase in human cells. This is likely to be a widely employed strategy, as UBF is present throughout metazoans. In higher eukaryotes, NORs are typically located within regions of chromosomes that form perinucleolar heterochromatin during interphase. Typically, the genomic architecture of NORs and the chromosomal regions within which they lie is very poorly described, yet recent evidence points to a role for context in their function. In Arabidopsis, NOR silencing appears to be controlled by sequences outside the rDNA (ribosomal DNA) array. Translocations reveal a role for context in the expression of the NOR on the X chromosome in Drosophila. Recent work has begun on characterizing the genomic architecture of human NORs. A role for distal sequences located in perinucleolar heterochromatin has been inferred, as they exhibit a complex transcriptionally active chromatin structure. Links between rDNA genomic stability and aging in Saccharomyces cerevisiae are now well established, and indications are emerging that this is important in aging and replicative senescence in higher eukaryotes. This, combined with the fact that rDNA arrays are recombinational hot spots in cancer cells, has focused attention on DNA damage responses in NORs. The introduction of DNA double-strand breaks into rDNA arrays leads to a dramatic reorganization of nucleolar structure. Damaged rDNA repeats move from the nucleolar interior to form caps at the nucleolar periphery, presumably to facilitate repair, suggesting that the chromosomal context of human NORs contributes to their genomic stability. The inclusion of NORs and their surrounding chromosomal environments in future genome drafts now becomes a priority.The relationship between nucleolar organizer regions (NORs) and nucleoli was first established in the 1930s (Heitz 1931;McClintock 1934), but, for decades, the content of the former and the role of the latter remained mysterious. The era of molecular and cellular biology revealed that NORs contain tandem arrays of ribosomal gene (rDNA) repeats and that nucleoli are the sites of ribosome biogenesis. Biochemistry has revealed the inner workings of the nucleolus and the complexity of ribosome biogenesis (for review, see Pederson 2010). However, the genomic architecture of NORs and the chromosomal context in which they lie remains undetermined for most eukaryotes. The resulting void has placed limitations on our understanding of the fundamental mechanisms by which NORs orchestrate formation of the largest structure in the nucleus. In this review, I discuss recent findings regarding the morphology of active NORs and how they seed r...

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Section: Rdna Arrays and Norsmentioning

confidence: 87%

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

2016

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“…In human, rDNA genes are encoded on chromosomes 13, 14, 15, 21 and 22 (Németh et al., 2010; Pederson, 2011). Importantly, the locations of rDNA genes can be strain-dependent in mice (Strongin et al, 2014; Suzuki et al, 1990). For instance, on chromosome 15, the 129 allele of the F1-21 hybrid mouse line does not include rDNA genes, while it does on the Cast allele (Strongin et al, 2014).…”

Section: Star Methodsmentioning

confidence: 99%

“…Importantly, the locations of rDNA genes can be strain-dependent in mice (Strongin et al, 2014; Suzuki et al, 1990). For instance, on chromosome 15, the 129 allele of the F1-21 hybrid mouse line does not include rDNA genes, while it does on the Cast allele (Strongin et al, 2014). This hybrid line was used for all DNA-DNA mapping methods and nucleolar hub identification.…”

Section: Star Methodsmentioning

confidence: 99%

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

Quinodoz

Ollikainen

Tabak

et al. 2018

Cell

773

814

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Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus.

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“…In the standard laboratory mouse strain, C57BL/6J, chromosomes 12 and 15 possess acrocentric rDNA arrays (aka nucleolar organizing centers or NORs) and thus localize preferentially near nucleoli. However, in other laboratory (and wild) mouse strains, one or both of these chromosomes do not contain an NOR (presumably due to the increased recombination rate between mouse acrocentric sequences) and in these strains, chromosomal territories 12 and 15 associate more frequently with the periphery (Figure 2D) [76]. It is unlikely that lamin A/lamin B1 ratios affect the proximity of an NOR bearing chromosome to a nucleolus, as can be proposed for the centromeric sequences above.…”

Section: Introductionmentioning

confidence: 99%

The redundancy of the mammalian heterochromatic compartment

Politz

Scalzo

Groudine

2016

Current Opinion in Genetics & Development

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Two chromatin compartments are present in most mammalian cells; the first contains primarily euchromatic, early replicating chromatin and the second, primarily late-replicating heterochromatin, which is the subject of this review. Heterochromatin is concentrated in three intranuclear regions: the nuclear periphery, the perinucleolar space and in pericentromeric bodies. We review recent evidence demonstrating that the heterochromatic compartment is critically involved in global nuclear organization and the maintenance of genome stability, and discuss models regarding how this compartment is formed and maintained. We also evaluate our understanding of how heterochromatic sequences (herein named heterochromatic associated regions (HADs)) might be tethered within these regions and review experiments that reveal the stochastic nature of individual HAD positioning within the compartment. These investigations suggest a substantial level of functional redundancy within the heterochromatic compartment.

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Nucleolar tethering mediates pairing between theIgHandMycloci

Cited by 17 publications

References 53 publications

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

Nucleolar organizer regions: genomic ‘dark matter’ requiring illumination

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

The redundancy of the mammalian heterochromatic compartment

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