Tissue-specific spatial organization of genomes

Parada, Luis Antonio; McQueen, Philip G.; Misteli, Tom

doi:10.1186/gb-2004-5-7-r44

Cited by 333 publications

(151 citation statements)

References 34 publications

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“…These interconnected changes occur within nuclei that harbor an altered 3D organization (1)(2)(3). In agreement with this concept, recent reports suggest tumor-associated changes of chromosomal organization in an altered 3D nucleus (3)(4)(5)(6)(7)(8). However, mechanisms leading to structural changes of telomeres and chromosomes remain elusive.…”

mentioning

confidence: 56%

c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus

Louis

Vermolen

Garini

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

144

204

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In previous work, we showed that telomeres of normal cells are organized within the 3D space of the interphase nucleus in a nonoverlapping and cell cycle-dependent manner. This order is distorted in tumor cell nuclei where telomeres are found in close association forming aggregates of various numbers and sizes. Here we show that c-Myc overexpression induces telomeric aggregations in the interphase nucleus. Directly proportional to the duration of c-Myc deregulation, we observe three or five cycles of telomeric aggregate formation in interphase nuclei. These cycles reflect the onset and propagation of breakage-bridge-fusion cycles that are initiated by end-to-end telomeric fusions of chromosomes. Subsequent to initial chromosomal breakages, new fusions follow and the breakage-bridge-fusion cycles continue. During this time, nonreciprocal translocations are generated. c-Myc-dependent remodeling of the organization of telomeres thus precedes the onset of genomic instability and subsequently leads to chromosomal rearrangements. Our findings reveal that c-Myc possesses the ability to structurally modify chromosomes through telomeric fusions, thereby reorganizing the genetic information.genomic instability ͉ 3D nucleus ͉ breakage-bridge-fusion

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mentioning

confidence: 56%

c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus

Louis

Vermolen

Garini

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

144

204

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“…Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian cells, (Bickmore 2013; Cremer and Cremer 2010; Lanctot et al 2007; Meaburn and Misteli 2007; Misteli 2004; Parada et al 2004a; Parada et al 2004b) our understanding of the global shape and 3-D organization of the individual CT remains very limited. With this in mind, we have undertaken a comprehensive analysis to determine the shape regularity of different CT in WI38 normal diploid human lung fibroblast cells.…”

Section: Resultsmentioning

confidence: 99%

Gene density and chromosome territory shape

et al. 2014

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Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian cells, our understanding of the global shape and 3-D organization of the individual CT remains very limited. Past microscopic analysis of CT suggested that, while many of the CT appear to be very regular ellipsoid-like shapes, there were also those with more irregular shapes. We have undertaken a comprehensive analysis to determine the degree of shape regularity of different CT. To be representative of the whole human genome, 12 different CT (~41% of the genome) were selected that ranged from the largest (CT 1) to the smallest (CT 21) in size and from the highest (CT 19) to lowest (CT Y) in gene density. Using both visual inspection and algorithms that measure the degree of shape ellipticity and regularity, we demonstrate a strong inverse correlation between the degree of regular CT shape and gene density for those CT that are most gene rich (19, 17, 11) and gene poor (18, 13, Y). CT more intermediate in gene density, showed a strong negative correlation with shape regularity but not with ellipticity. An even more striking correlation between gene density and CT shape was determined for the nucleolar associated NOR-CT. Correspondingly striking differences in shape between the X active and inactive CT implied that, aside from gene density, the overall global level of gene transcription on individual CT is also an important determinant of chromosome territory shape.

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“…Mammalian chromosomes reside in distinct regions of the nucleus termed chromosome territories. [15][16][17][18][19] These territories are not disjunct and a degree of chromosome mixing occurs. 18 So far, the existence of chromosome territories within the budding yeast nucleus is debated 20,21 although there is growing evidence of their existence.…”

Section: Chromosome Positioning and The Clustering Of Functionally Rementioning

confidence: 99%

Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions

Gehlen

Gruenert

Jones

et al. 2012

Nucleus

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Tissue-specific spatial organization of genomes

Cited by 333 publications

References 34 publications

c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus

c-Myc induces chromosomal rearrangements through telomere and chromosome remodeling in the interphase nucleus

Gene density and chromosome territory shape

Chromosome positioning and the clustering of functionally related loci in yeast is driven by chromosomal interactions

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