Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes

By A. Bolzer, G. Kreth, Irina Solovei, D. Koehler, Kaan Saracoglu, Christine Fauth, S. Müller, Roland Eils, Christoph Cremer, M. R. Speicher and 1 more. PLoS Biology, 2005

833 citations recorded by the source corpus.

Studies of higher-order chromatin arrangements are an essential part of ongoing attempts to explore changes in epigenome structure and their functional implications during development and cell differentiation. However, the extent and cell-type-specificity of three-dimensional (3D) chromosome arrangements has remained controversial. In order to overcome technical limitations of previous studies, we have developed tools that allow the quantitative 3D positional mapping of all chromosomes simultaneously. We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs) in nuclei of quiescent (G0) and cycling (early S-phase) human diploid fibroblasts (46, XY). Radial distance measurements showed a probabilistic, highly nonrandom correlation with chromosome size: small chromosomes—independently of their gene density—were distributed significantly closer to the center of the nucleus or prometaphase rosette, while large chromosomes were located closer to the nuclear or rosette rim. This arrangement was independently confirmed in both human fibroblast and amniotic fluid cell nuclei. Notably, these cell types exhibit flat-ellipsoidal cell nuclei, in contrast to the spherical nuclei of lymphocytes and several other human cell types, for which we and others previously demonstrated gene-density-correlated radial 3D CT arrangements. Modeling of 3D CT arrangements suggests that cell-type-specific differences in radial CT arrangements are not solely due to geometrical constraints that result from nuclear shape differences. We also found gene-density-correlated arrangements of higher-order chromatin shared by all human cell types studied so far. Chromatin domains, which are gene-poor, form a layer beneath the nuclear envelope, while gene-dense chromatin is enriched in the nuclear interior. We discuss the possible functional implications of this finding.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/88e1f90aef284d290b9d309c9ee18baafaaf922b

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Citations in the corpus

Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions (2007, background): “It is now also known that individual chromosomes occupy distinct positions in the nucleus, referred to as chromosome territorie”
Chromatin in pluripotent embryonic stem cells and differentiation (2006, background): “These preferential positions are probably functionally important as they vary among tissues, during development and among cell type”
Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells (2009, background): “In higher eukaryotes individual chromosomes occupy discrete chromosome territories in the three-dimensional space of the nucleu”
CTCF-Mediated Functional Chromatin Interactome in Pluripotent Cells (2011, background): “(3) Generating empirical negative controls of CTCF loops.”
A decade of 3C technologies: insights into nuclear organization. (2012, background): “Microscopy observations into mammalian genome organization Chromosomes occupy their own territory in the cell nucleus (Cremer et al. 1982; Bolzer et al. 2005; Cremer and Cremer 2006) and adopt a preferential radial position within the nucleus, with large chromosomes found more often at the nuclear…”
Structure and Dynamics of Interphase Chromosomes (2008, methodology): “The localization of territories inside the nucleus exhibits regular patterns: gene-rich chromosomes in human lymphocytes preferably locate in the nuclear interior while gene-poor chromosomes are typically found closer to the periphery [12,13]; in contrast, in human fibroblasts positioning of territo”
Chromosome territories. (2010, background): “Whereas little evidence for nonrandom neighborhood/proximity patterns was found between specific homologous and heterologous chromosomes in nuclei of human fibroblasts (Bolzer et al. 2005), nonrandom proximity patterns for smaller subsets of nonhomologous CTs were described by Misteli and coworkers ”
Beyond the sequence: cellular organization of genome function. (2007, neutral): “Although similar correlations have been made in other cell types, chromosome positioning has been correlated with properties other than gene density, such as chromosome size (Bolzer et al., 2005).”
Nuclear organization of the genome and the potential for gene regulation (2007, background): “Chromosomes have preferred positions with respect to the centre or periphery of the nucleu”