Inheritance of gene density–related higher order chromatin arrangements in normal and tumor cell nuclei

Cremer, Marion; Küpper, Katrin; Wagler, Babett; Wizelman, Leah; Hase, Johann von; Weiland, Yanina; Kreja, Ludwika; Diebold, Joachim; Speicher, Michael R.; Cremer, Thomas

doi:10.1083/jcb.200304096

Cited by 232 publications

(234 citation statements)

References 37 publications

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“…Unlike the localization of chromosomes in fibroblasts, in the more spherical lymphocyte cells gene density also influences chromosome positioning. 17,[20][21][22] This behavior is reflected by the peripheral association of late replicating loci on the similarly sized chromosome pairs chr19 and chr20 (59, 64 Mb), and chr21 and chr22 (47, 51 Mb). In both cases the loci on the gene poorer chromosome (chr20 and chr21) associated 2-3 times more frequently with the lamina than on those on the gene denser chromosome (chr19 and chr22), suggesting a generally more peripheral localization of the whole chromosome.…”

Section: Discussionmentioning

confidence: 99%

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

Ragoczy

Telling

Scalzo

et al. 2014

Nucleus

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The eukaryotic nucleus is structurally and functionally organized, as reflected in the distribution of its protein and DNA components. The genome itself is segregated into euchromatin and heterochromatin that replicate in a distinct spatio-temporal manner. We used a combination of fluorescence in situ hybridization (FISH) and DamID to investigate the localization of the early and late replicating components of the genome in a lymphoblastoid cell background. Our analyses revealed that the bulk of late replicating chromatin localizes to the nuclear peripheral heterochromatin (PH) in a chromosome size and gene density dependent manner. Late replicating DNA on small chromosomes exhibits a much lower tendency to localize to PH and tends to associate with alternate repressive subcompartments such as pericentromeric (PCH) and perinucleolar heterochromatin (PNH). Furthermore, multicolor FISH analysis revealed that late replicating loci, particularly on the smaller chromosomes, may associate with any of these 3 repressive subcompartments, including more than one at the same time. These results suggest a functional equivalence or redundancy among the 3 subcompartments. Consistent with this notion, disruption of nucleoli resulted in an increased association of late replicating loci with peripheral heterochromatin. Our analysis reveals that rather than considering the morphologically distinct PH, PCH and PNH as individual subcompartments, they should be considered in aggregate as a functional compartment for late replicating chromatin.

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Section: Discussionmentioning

confidence: 99%

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

Ragoczy

Telling

Scalzo

et al. 2014

Nucleus

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“…For example, while chromosomes in cancer cell lines with near-normal karyotypes are generally positioned according to their gene density, up to 31% of nuclei in some of these lines contain an inverted pattern of chromosomes 18 and 19 [25]. A similar inversion of chromosomes 18 and 19 has been found in about onethird of papillary thyroid carcinoma cells but not in normal thyroid cells [26].…”

Section: Nuclear Organization In Normal and Cancer Cellsmentioning

confidence: 99%

The role of nuclear organization in cancer

Lever¹,

Sheer²

2009

The Journal of Pathology

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The functional significance of changes in nuclear structure and organization in transformed cells remains one of the most enigmatic questions in cancer biology. In this review, we discuss relationships between nuclear organization and transcription in terms of the threedimensional arrangement of genes in the interphase cancer nucleus and the regulatory functions of nuclear matrix proteins. We also analyse the role of nuclear topology in the generation of gene fusions. We speculate that this type of multi-layered analysis will one day provide a framework for a more comprehensive understanding of the genetic origins of cancer and the identification of new therapeutic targets.

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“…2c) (Cremer, et al 2003;Sengupta, et al 2007). This was confirmed through a comparison of the median radial distances of HSA18 in A9+18 (M = 73.40), DLD-1 (M = 72.69) and DLD-1+18 (M = 74.07) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The homogeneously sized chromosomes of the primate species Wolf's Guenon are distinctly positioned with gene dense chromosomes predominantly in the nuclear center (Neusser, et al 2007). Both 2D and 3D-FISH analyses of cells containing translocation chromosomes show that the more gene dense partner is predominantly more centrally positioned than the gene poor partner (Croft et al 1999, Cremer et al 2003. Flat human fibroblasts showed a higher density of Alu rich sequences, typically found in the gene dense R-bands of chromosomes, in the center of the nucleus, suggesting that while size may have had a greater influence on territory positioning, gene density based correlations are relevant and might be crucial in establishing non-random chromosome positioning patterns (Bolzer, et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Position of human chromosomes is conserved in mouse nuclei indicating a species-independent mechanism for maintaining genome organization

et al. 2008

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The non-random positioning of chromosome territories in eukaryotic cells is largely correlated with gene density and is conserved throughout evolution. Gene rich chromosomes are predominantly central while gene poor chromosomes are peripherally localized in interphase nuclei. We previously demonstrated that artificially introduced human chromosomes assume a position equivalent to their endogenous homologues in the diploid colon cancer cell line DLD-1. These chromosomal aneuploidies result in a significant increase in transcript levels, suggesting a relationship between genomic copy number, gene expression and chromosome position. We previously proposed that each chromosome is marked by a "zip-code" that determines its non-random position in the nucleus. Here we investigated (1) whether mouse nuclei recognize such determinants of nuclear position on human chromosomes to facilitate their distinct partitioning and (2) if chromosome positioning and transcriptional activity remain coupled under these trans-species conditions. Using 3D-FISH, confocal microscopy and gene expression profiling, we show (i) that gene poor and gene rich human chromosomes maintain their divergent but conserved positions in mouse-human hybrid nuclei and (ii) that a foreign human chromosome is actively transcribed in mouse nuclei. Our results suggest a species-independent conserved mechanism for the non-random positioning of chromosomes in the 3-dimensional interphase nucleus.

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Inheritance of gene density–related higher order chromatin arrangements in normal and tumor cell nuclei

Cited by 232 publications

References 37 publications

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

Functional redundancy in the nuclear compartmentalization of the late-replicating genome

The role of nuclear organization in cancer

Position of human chromosomes is conserved in mouse nuclei indicating a species-independent mechanism for maintaining genome organization

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