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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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Related in: MedlinePlus

Quantitative 3D evaluation in the different cell types of radial CT #18 and CT #19 distribution in 25 concentric nuclear shells after painting with DNA probes specific for chromosome 18 (red) and chromosome 19 (green). Blue curves represent counterstained DNA. 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. For normalization, the area underlying the curve for each color (total relative DNA content) was set to 100. Note the different curve for the DNA counterstain obtained in nuclei of cultivated cells (A–F, H, and K–N) and in nuclei obtained from tissue sections (G, I, and J). For explanation, see Materials and methods. All graphs show the different radial positioning of CT # 18 and CT #19 material. Bars indicate SEM.
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fig2: Quantitative 3D evaluation in the different cell types of radial CT #18 and CT #19 distribution in 25 concentric nuclear shells after painting with DNA probes specific for chromosome 18 (red) and chromosome 19 (green). Blue curves represent counterstained DNA. 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. For normalization, the area underlying the curve for each color (total relative DNA content) was set to 100. Note the different curve for the DNA counterstain obtained in nuclei of cultivated cells (A–F, H, and K–N) and in nuclei obtained from tissue sections (G, I, and J). For explanation, see Materials and methods. All graphs show the different radial positioning of CT # 18 and CT #19 material. Bars indicate SEM.

Mentions: Fig. 2 shows the curves for the distribution of chromosome 18–specific (red) and chromosome 19–specific (green) chromatin and for the nuclear counterstain (blue). For each cell type, 11–38 nuclei were evaluated. In each graph, the normalized DNA content, represented by its voxel intensity–weighted fluorochromes, is plotted against the relative radius within a nucleus (for details see Materials and methods). Thus, these curves explore the positioning of these CTs with regard to their distance from the geometrical center of the nucleus. We refer to this correlation as “radial chromatin arrangement.” 3D reconstructions of selected nuclei are displayed in Fig. 3.


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)

Quantitative 3D evaluation in the different cell types of radial CT #18 and CT #19 distribution in 25 concentric nuclear shells after painting with DNA probes specific for chromosome 18 (red) and chromosome 19 (green). Blue curves represent counterstained DNA. 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. For normalization, the area underlying the curve for each color (total relative DNA content) was set to 100. Note the different curve for the DNA counterstain obtained in nuclei of cultivated cells (A–F, H, and K–N) and in nuclei obtained from tissue sections (G, I, and J). For explanation, see Materials and methods. All graphs show the different radial positioning of CT # 18 and CT #19 material. Bars indicate SEM.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Quantitative 3D evaluation in the different cell types of radial CT #18 and CT #19 distribution in 25 concentric nuclear shells after painting with DNA probes specific for chromosome 18 (red) and chromosome 19 (green). Blue curves represent counterstained DNA. 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. For normalization, the area underlying the curve for each color (total relative DNA content) was set to 100. Note the different curve for the DNA counterstain obtained in nuclei of cultivated cells (A–F, H, and K–N) and in nuclei obtained from tissue sections (G, I, and J). For explanation, see Materials and methods. All graphs show the different radial positioning of CT # 18 and CT #19 material. Bars indicate SEM.
Mentions: Fig. 2 shows the curves for the distribution of chromosome 18–specific (red) and chromosome 19–specific (green) chromatin and for the nuclear counterstain (blue). For each cell type, 11–38 nuclei were evaluated. In each graph, the normalized DNA content, represented by its voxel intensity–weighted fluorochromes, is plotted against the relative radius within a nucleus (for details see Materials and methods). Thus, these curves explore the positioning of these CTs with regard to their distance from the geometrical center of the nucleus. We refer to this correlation as “radial chromatin arrangement.” 3D reconstructions of selected nuclei are displayed in Fig. 3.

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