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

Cremer M, Küpper K, Wagler B, Wizelman L, von Hase J, Weiland Y, Kreja L, Diebold J, Speicher MR, Cremer T - J. Cell Biol. (2003)

Bottom Line: Bickmore. 1999.Cell Biol. 145:1119-1131).Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology II, Ludwig Maximilians University, 80333 Munich, Germany. Marion.Cremer@lrz.uni-muenchen.de

ABSTRACT
A gene density-related difference in the radial arrangement of chromosome territories (CTs) was previously described for human lymphocyte nuclei with gene-poor CT #18 located toward the nuclear periphery and gene-dense CT #19 in the nuclear interior (Croft, J.A., J.M. Bridger, S. Boyle, P. Perry, P. Teague, and W.A. Bickmore. 1999. J. Cell Biol. 145:1119-1131). Here, we analyzed the radial distribution of chromosome 18 and 19 chromatin in six normal cell types and in eight tumor cell lines, some of them with imbalances and rearrangements of the two chromosomes. Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types. However, in seven of eight tumor cell lines, the difference was less pronounced compared with normal cell nuclei due to a higher fraction of nuclei showing an inverted CT position, i.e., a CT #18 located more internally than a CT #19. This observation emphasizes a partial loss of radial chromatin order in tumor cell nuclei.

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Evaluation of CT #17 and CT #18 distribution of the SW620 cell line carrying a translocation t(17;18). (A) Part of a metaphase spread after painting of chromosome 17 (visualized in blue) and chromosome 18 (visualized in green). The chromosome 18 centromere is visualized in red. In the metaphase shown, chromosome 17 is present as two free, normal copies and as two different translocation chromosomes, one of them forming the der(18)t(17;18) (arrow). The centromere of this rearranged chromosome is chromosome 18 specific. Chromosome 18 is also present as one normal copy. (B) Quantitative 3D evaluation of the radial CT #17 and CT #18 distribution in 22 nuclei. The abscissa denotes the relative radius r of the nuclear shells, the ordinate the normalized sum of intensities in the voxels for a respective fluorochrome assigned to a given shell. In the top panel, the dark blue curve denotes the radial distribution of the entire chromosome 17 material after painting with a DNA probe specific for chromosome 17, and the light blue curve denotes only chromosome 17 material translocated to chromosome 18. Note the almost identical curves for both fractions of CT #17 material. In the bottom panel, the dark green curve denotes the radial distribution of free CTs #18, and the light green curve denotes chromosome 18 material translocated to chromosome 17. Note the distinctly more peripheral positioning of the nontranslocated fraction of CTs #18 in comparison to the translocated fraction. Bars indicate SEM.
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fig4: Evaluation of CT #17 and CT #18 distribution of the SW620 cell line carrying a translocation t(17;18). (A) Part of a metaphase spread after painting of chromosome 17 (visualized in blue) and chromosome 18 (visualized in green). The chromosome 18 centromere is visualized in red. In the metaphase shown, chromosome 17 is present as two free, normal copies and as two different translocation chromosomes, one of them forming the der(18)t(17;18) (arrow). The centromere of this rearranged chromosome is chromosome 18 specific. Chromosome 18 is also present as one normal copy. (B) Quantitative 3D evaluation of the radial CT #17 and CT #18 distribution in 22 nuclei. The abscissa denotes the relative radius r of the nuclear shells, the ordinate the normalized sum of intensities in the voxels for a respective fluorochrome assigned to a given shell. In the top panel, the dark blue curve denotes the radial distribution of the entire chromosome 17 material after painting with a DNA probe specific for chromosome 17, and the light blue curve denotes only chromosome 17 material translocated to chromosome 18. Note the almost identical curves for both fractions of CT #17 material. In the bottom panel, the dark green curve denotes the radial distribution of free CTs #18, and the light green curve denotes chromosome 18 material translocated to chromosome 17. Note the distinctly more peripheral positioning of the nontranslocated fraction of CTs #18 in comparison to the translocated fraction. Bars indicate SEM.

Mentions: Fig. 4 illustrates the shift of CT positions caused by a translocation event. Average relative radii (see Materials and methods) for all normal and malignant cell types are summarized in Fig. 5 and were used for a comparison of CT distribution between different cell types.


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

Cremer M, Küpper K, Wagler B, Wizelman L, von Hase J, Weiland Y, Kreja L, Diebold J, Speicher MR, Cremer T - J. Cell Biol. (2003)

Evaluation of CT #17 and CT #18 distribution of the SW620 cell line carrying a translocation t(17;18). (A) Part of a metaphase spread after painting of chromosome 17 (visualized in blue) and chromosome 18 (visualized in green). The chromosome 18 centromere is visualized in red. In the metaphase shown, chromosome 17 is present as two free, normal copies and as two different translocation chromosomes, one of them forming the der(18)t(17;18) (arrow). The centromere of this rearranged chromosome is chromosome 18 specific. Chromosome 18 is also present as one normal copy. (B) Quantitative 3D evaluation of the radial CT #17 and CT #18 distribution in 22 nuclei. The abscissa denotes the relative radius r of the nuclear shells, the ordinate the normalized sum of intensities in the voxels for a respective fluorochrome assigned to a given shell. In the top panel, the dark blue curve denotes the radial distribution of the entire chromosome 17 material after painting with a DNA probe specific for chromosome 17, and the light blue curve denotes only chromosome 17 material translocated to chromosome 18. Note the almost identical curves for both fractions of CT #17 material. In the bottom panel, the dark green curve denotes the radial distribution of free CTs #18, and the light green curve denotes chromosome 18 material translocated to chromosome 17. Note the distinctly more peripheral positioning of the nontranslocated fraction of CTs #18 in comparison to the translocated fraction. Bars indicate SEM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172812&req=5

fig4: Evaluation of CT #17 and CT #18 distribution of the SW620 cell line carrying a translocation t(17;18). (A) Part of a metaphase spread after painting of chromosome 17 (visualized in blue) and chromosome 18 (visualized in green). The chromosome 18 centromere is visualized in red. In the metaphase shown, chromosome 17 is present as two free, normal copies and as two different translocation chromosomes, one of them forming the der(18)t(17;18) (arrow). The centromere of this rearranged chromosome is chromosome 18 specific. Chromosome 18 is also present as one normal copy. (B) Quantitative 3D evaluation of the radial CT #17 and CT #18 distribution in 22 nuclei. The abscissa denotes the relative radius r of the nuclear shells, the ordinate the normalized sum of intensities in the voxels for a respective fluorochrome assigned to a given shell. In the top panel, the dark blue curve denotes the radial distribution of the entire chromosome 17 material after painting with a DNA probe specific for chromosome 17, and the light blue curve denotes only chromosome 17 material translocated to chromosome 18. Note the almost identical curves for both fractions of CT #17 material. In the bottom panel, the dark green curve denotes the radial distribution of free CTs #18, and the light green curve denotes chromosome 18 material translocated to chromosome 17. Note the distinctly more peripheral positioning of the nontranslocated fraction of CTs #18 in comparison to the translocated fraction. Bars indicate SEM.
Mentions: Fig. 4 illustrates the shift of CT positions caused by a translocation event. Average relative radii (see Materials and methods) for all normal and malignant cell types are summarized in Fig. 5 and were used for a comparison of CT distribution between different cell types.

Bottom Line: Bickmore. 1999.Cell Biol. 145:1119-1131).Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology II, Ludwig Maximilians University, 80333 Munich, Germany. Marion.Cremer@lrz.uni-muenchen.de

ABSTRACT
A gene density-related difference in the radial arrangement of chromosome territories (CTs) was previously described for human lymphocyte nuclei with gene-poor CT #18 located toward the nuclear periphery and gene-dense CT #19 in the nuclear interior (Croft, J.A., J.M. Bridger, S. Boyle, P. Perry, P. Teague, and W.A. Bickmore. 1999. J. Cell Biol. 145:1119-1131). Here, we analyzed the radial distribution of chromosome 18 and 19 chromatin in six normal cell types and in eight tumor cell lines, some of them with imbalances and rearrangements of the two chromosomes. Our findings demonstrate that a significant difference in the radial distribution of #18 and #19 chromatin is a common feature of higher order chromatin architecture in both normal and malignant cell types. However, in seven of eight tumor cell lines, the difference was less pronounced compared with normal cell nuclei due to a higher fraction of nuclei showing an inverted CT position, i.e., a CT #18 located more internally than a CT #19. This observation emphasizes a partial loss of radial chromatin order in tumor cell nuclei.

Show MeSH
Related in: MedlinePlus