Ribosomal genes in inbred mouse strains: Interstrain and intrastrain variation of copy number and extent of methylation

Veiko, Natalia N.; Shubaeva, N. O.; Malashenko, A. M.; Бескова, Т. Б.; Agapova, R. K.; Lyapunova, N. A.

doi:10.1134/s1022795407090086

Cited by 8 publications

(6 citation statements)

References 37 publications

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“…1A ). 28 - 32 We isolated mature resting B-cells from the spleens of C57, CBA, and 129P3 mice and performed DNA immunofluorescence (immunoFISH) using whole chromosome paints of Chr 12 and Chr 15 along with an antibody to label nucleoli ( Fig. 1B ; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We observed that previous studies relied on BALB/c and C57BL/6 (C57) mice, where both Chr 12 and Chr 15 carry NORs. 25 , 26 , 28 - 32 We hypothesized that tethering Chr 12 and Chr 15 to the same nucleolus via their NORs could explain both the chromosome proximity and IgH:Myc colocalization frequency. An alternate possibility was that this colocalization was driven by factors unrelated to NOR-tethering.…”

Section: Introductionmentioning

confidence: 99%

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Nucleolar tethering mediates pairing between theIgHandMycloci

Strongin

Groudine

Politz

2014

Nucleus

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Gene loci on different chromosomes can preferentially colocalize in the cell nucleus. However, many of the mechanisms mediating this spatial proximity remain to be elucidated. The IgH locus on Chromosome 12 and the Myc locus on Chromosome 15 are a well-studied model for gene colocalization in murine B cells, where the two loci are positioned in close proximity at a higher than expected frequency. These gene loci are also partners in the chromosomal translocation that causes murine plasmacytoma and Burkitt’s lymphoma. Because both Chromosome 12 and Chromosome 15 carry nucleolar organizer regions (NORs) in the most commonly studied mouse strains, we hypothesized that NOR-mediated tethering of the IgH and Myc loci to shared nucleoli could serve as a mechanism to drive IgH:Myc colocalization. Using mouse strains that naturally carry nucleolar organizer regions (NORs) on different sets of chromosomes, we establish that IgH and Myc are positioned proximal to nucleoli in a NOR dependent manner and show that their joint association with nucleoli significantly increases the frequency of IgH and Myc pairing. Thus we demonstrate that simple nucleolar tethering can increase the colocalization frequency of genes on NOR-bearing chromosomes.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nucleolar tethering mediates pairing between theIgHandMycloci

Strongin

Groudine

Politz

2014

Nucleus

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“…Future work could study different species and/or different environmental stressors, such as nutrient stress 92 or exposure to pollutants 52 , to uncover possible drivers of rDNA copy number variation in teleosts. Nonetheless, it is interesting that directional selection on body size affected rDNA copy number as significant differences in rDNA copy number among strains of inbred laboratory mice ( Mus musculus 93 ) raise the prospect that rDNA copy number might be impacted by reductions in population size/inbreeding (as discussed for telomere length). Indeed, the significant positive correlation between rDNA and relative telomere length supports the idea that these regions are sensitive to similar stressors 94 .…”

Section: Discussionmentioning

confidence: 99%

Directional selection, not the direction of selection, affects telomere length and copy number at ribosomal RNA loci

Sadler,

Watts,

Uusi-Heikkilä

2024

Sci Rep

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Many fisheries exert directional selection on traits such as body size and growth rate. Whether directional selection impacts regions of the genome associated with traits related to growth is unknown. To address this issue, we characterised copy number variation in three regions of the genome associated with cell division, (1) telomeric DNA, (2) loci transcribed as ribosomal RNA (rDNA), and (3) mitochondrial DNA (mtDNA), in three selection lines of zebrafish reared at three temperatures (22 °C, 28 °C, and 34 °C). Selection lines differed in (1) the direction of selection (two lines experienced directional selection for large or small body size) and (2) whether they experienced any directional selection itself. Lines that had experienced directional selection were smaller, had lower growth rate, shorter telomeres, and lower rDNA copy number than the line that experiencing no directional selection. Neither telomere length nor rDNA copy number were affected by temperature. In contrast, mtDNA content increased at elevated temperature but did not differ among selection lines. Though directional selection impacts rDNA and telomere length, direction of such selection did not matter, whereas mtDNA acts as a stress marker for temperature. Future work should examine the consequences of these genomic changes in natural fish stocks.

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“…We tested the effects of metformin at significantly lower doses (1 mM or less) than have been reported by many other investigators in pre-clinical studies (generally 5-30 mM). Although achieving such levels of metformin in plasma remains a challenge, it is transported into cells by the organic cation transporter 1-3 (OCT1-3), which can be highly expressed in prostate tissue and may allow for enhanced intracellular drug accumulation [45,46].…”

Section: Discussionmentioning

confidence: 99%

Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells

Xie

Wang

Khan

et al. 2021

Cancers

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We explored whether the anti-prostate cancer (PC) activity of the androgen receptor-axis-targeted agents (ARATs) abiraterone and enzalutamide is enhanced by metformin. Using complementary biological and molecular approaches, we determined the associated underlying mechanisms in pre-clinical androgen-sensitive PC models. ARATs increased androgren receptors (ARs) in LNCaP and AR/ARv7 (AR variant) in VCaP cells, inhibited cell proliferation in both, and induced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage and death in VCaP but not LNCaP cells. Metformin decreased AR and ARv7 expression and induced cleaved PARP-1-associated death in both cell lines. Metformin with abiraterone or enzalutamide decreased AR and ARv7 expression showed greater inhibition of cell proliferation and greater induction of cell death than single agent treatments. Combination treatments led to increased cleaved PARP-1 and enhanced PARP-1 activity manifested by increases in poly(ADP-ribose) (PAR) and nuclear accumulation of apoptosis inducing factor (AIF). Enhanced annexin V staining occurred in LNCaP cells only with metformin/ARAT combinations, but no caspase 3 recruitment occurred in either cell line. Finally, metformin and metformin/ARAT combinations increased lysosomal permeability resulting in cathepsin G-mediated PARP-1 cleavage and cell death. In conclusion, metformin enhances the efficacy of abiraterone and enzalutamide via two PARP-1-dependent, caspase 3-independent pathways, providing a rationale to evaluate these combinations in castration-sensitive PC.

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Ribosomal genes in inbred mouse strains: Interstrain and intrastrain variation of copy number and extent of methylation

Cited by 8 publications

References 37 publications

Nucleolar tethering mediates pairing between theIgHandMycloci

Nucleolar tethering mediates pairing between theIgHandMycloci

Directional selection, not the direction of selection, affects telomere length and copy number at ribosomal RNA loci

Metformin and Androgen Receptor-Axis-Targeted (ARAT) Agents Induce Two PARP-1-Dependent Cell Death Pathways in Androgen-Sensitive Human Prostate Cancer Cells

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