Chromosome territories – a functional nuclear landscape

Cremer, Marion; Dietzel, Steffen; Müller, Stefan; Solovei, Irina; Fakan, Stanislav

doi:10.1016/j.ceb.2006.04.007

Cited by 542 publications

(486 citation statements)

References 79 publications

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“…It cannot be entirely excluded at this point that the latter is a surrogate for the total cellular deficit and that the PIC acquires p75 earlier, perhaps in inter-chromatin space [159] or even prior to nuclear entry as was suggested by PIC co-immunoprecipitation [75]. The lack of detail on this question parallels the larger ignorance about whether retroviral PICs negotiate intra-nuclear transit by specific directional processes or by random diffusion.…”

Section: Modeling P75 Function In the Hiv Life Cyclementioning

confidence: 96%

Integrase, LEDGF/p75 and HIV replication

Poeschla

2008

Cell. Mol. Life Sci.

115

104

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HIV integrates a DNA copy of its genome into a host cell chromosome in each replication cycle. The essential DNA cleaving and joining chemistry of integration is known, but there is less understanding of the process as it occurs in a cell, where two complex and dynamic macromolecular entities are joined: the viral pre-integration complex and chromatin. Among implicated cellular factors, much recent attention has coalesced around LEDGF/p75, a nuclear protein that may act as a chromatin docking factor or receptor for lentiviral pre-integration complexes. LEDGF/p75 tethers HIV integrase to chromatin, protects it from degradation, and strongly influences the genome-wide pattern of HIV integration. Depleting the protein from cells and/or over-expressing its integrase-binding domain blocks viral replication. Current goals are to establish the underlying mechanisms and to determine whether this knowledge can be exploited for antiviral therapy or for targeting lentiviral vector integration in human gene therapy.

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Section: Modeling P75 Function In the Hiv Life Cyclementioning

confidence: 96%

Integrase, LEDGF/p75 and HIV replication

Poeschla

2008

Cell. Mol. Life Sci.

115

104

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“…Gene-rich as well as small chromosomes are preferentially at internal positions and gene-poor or large chromosomes at peripheral positions (for reviews, see Foster and Bridger 2005;Cremer et al 2006;Lanctôt et al 2007). Homologous association as observed in Drosophila can be excluded as a general theme in mammals, since numerous FISH studies found two distinct chromosome territories in interphase nuclei.…”

Section: Introductionmentioning

confidence: 99%

Parental genomes mix in mule and human cell nuclei

et al. 2009

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Whether chromosome sets inherited from father and mother occupy separate spaces in the cell nucleus is a question first asked over 110 years ago. Recently, the nuclear organization of the genome has come increasingly into focus as an important level of epigenetic regulation. In this context, it is indispensable to know whether or not parental genomes are spatially separated. Genome separation had been demonstrated for plant hybrids and for the early mammalian embryo. Conclusive studies for somatic mammalian cell nuclei are lacking because homologous chromosomes from the two parents cannot be distinguished within a species. We circumvented this problem by investigating the three-dimensional distribution of chromosomes in mule lymphocytes and fibroblasts. Genomic DNA of horse and donkey was used as probes in fluorescence in situ hybridization under conditions where only tandem repetitive sequences were detected. We thus could determine the distribution of maternal and paternal chromosome sets in structurally preserved interphase nuclei for the first time. In addition, we investigated the distribution of several pairs of chromosomes in human bilobed granulocytes. Qualitative and quantitative image evaluation did not reveal any evidence for the separation of parental genomes. On the contrary, we observed mixing of maternal and paternal chromosome sets.

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“…Apart from molecular factors binding directly to DNA and changes in the local chromatin environment, the nuclear organization of chromatin has come into focus as a potential level of genome regulation (for reviews see Kosak and Groudine 2004;Foster and Bridger 2005;Cremer et al 2006;Fraser and Bickmore 2007;Lanctôt et al 2007;Meaburn and Misteli 2007;Misteli 2007). To understand this level of genome organization, it is essential to know the three-dimensional distribution of the genome.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional positioning of genes in mouse cell nuclei

et al. 2008

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To understand the regulation of the genome, it is necessary to understand its three-dimensional organization in the nucleus. We investigated the positioning of eight gene loci on four different chromosomes, including the β-globin gene, in mouse embryonic stem cells and in in vitro differentiated macrophages by fluorescence in situ hybridization on structurally preserved nuclei, confocal microscopy, and 3D quantitative image analysis. We found that gene loci on the same chromosome can significantly differ from each other and from their chromosome territory in their average radial nuclear position. Radial distribution of a given gene locus can change significantly between cell types, excluding the possibility that positioning is determined solely by the DNA sequence. For the set of investigated gene loci, we found no relationship between radial distribution and local gene density, as it was described for human cell nuclei. We did find, however, correlation with other genomic properties such as GC content and certain repetitive elements such as long terminal repeats or long interspersed nuclear elements. Our results suggest that gene density itself is not a driving force in nuclear positioning. Instead, we propose that other genomic properties play a role in determining nuclear chromatin distribution.

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Chromosome territories – a functional nuclear landscape

Cited by 542 publications

References 79 publications

Integrase, LEDGF/p75 and HIV replication

Integrase, LEDGF/p75 and HIV replication

Parental genomes mix in mule and human cell nuclei

Three-dimensional positioning of genes in mouse cell nuclei

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