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Evolutionarily conserved, cell type and species-specific higher order chromatin arrangements in interphase nuclei of primates

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Abstract

Several studies demonstrated a gene-density-correlated radial organization of chromosome territories (CTs) in spherically shaped nuclei of human lymphocytes or lymphoblastoid cells, while CT arrangements in flat-ellipsoidal nuclei of human fibroblasts are affected by both gene density and chromosome size. In the present study, we performed fluorescence in situ hybridization (FISH) experiments to three-dimensionally preserved nuclei (3D-FISH) from human and nonhuman primate cultured lymphoblastoid cells and fibroblasts. We investigated apes, Old, and New World monkeys showing either evolutionarily conserved karyotypes, multiple translocations, fusions, or serial fissions. Our goal was to test whether cell type specific differences of higher order chromatin arrangements are evolutionarily conserved in different primate lineages. Whole genome painting experiments and further detailed analyses of individual chromosomes indicate a gene-density-correlated higher order organization of chromatin in lymphoblastoid cell nuclei of all studied primate species, despite evolutionary chromosome reshuffling. In contrast, in primate fibroblast nuclei evolutionary translocations, fissions and fusions resulted in positional shifts of orthologous chromosome segments, thus arguing against a functional role of chromosome size-dependent spatial chromatin arrangements and for geometrical constraints in flat-ellipsoidal fibroblast nuclei. Notably, in both cell types, regions of rearranged chromosomes with distinct differences in gene density showed polarized arrangements with the more gene-dense segment oriented towards the nuclear interior. Our results indicate that nonrandom breakage and rejoining of preferentially gene-dense chromosomes or chromosome segments may have occurred during evolution.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft grant MU 1850/2-1. We thank Marion Cremer, Ludwig-Maximilians-University Munich, for the fruitful discussions.

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Correspondence to Stefan Müller.

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Communicated by E.A. Nigg

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Supplementary Figure 1

Additional FISH experiments to human and non-human primate metaphases exemplifying the pattern of chromosome rearrangements in the species investigated and outlining the probe composition used in subsequent 3D-FISH experiments (scale bar = 10 μm). 24 color M-FISH karyotyping illustrates A) multiple, complex translocations in the gibbon and B) serial fissions in Wolf’s guenon. C) human and D) orangutan chromosomes hybridized with pooled human whole chromosome and arm paint probes which were differentially labeled according to their gene density - gene-dense (blue), intermediate (red) and gene-poor (green). E) Pooled and differentially labeled human paint probes for chromosome 1, 3–6 (blue), 16–20 (green) and for human NOR bearing chromosomes 13–15, 21, 22 (red), hybridized to human metaphases. F) Human and G) gorilla metaphase hybridized with probes specific for 2pter-q13 (red) and 2q13-qter (green). H) Human and I) marmoset metaphase hybridized with 1p34-pter (green) and 1q32-qter (red) probes (DOC 811 kb)

Supplementary Figure 2

Overrepresentation of gene-dense human homologous chromosome segments in translocations during gibbon evolution. When dividing human chromosomes into three different classes of approx. 1Gbp each according to their gene density (NCBI build 35.1; http://www.ncbi.nlm.nih.gov), see Supplementary Table 1), from the 95 inter-chromosomal rearrangements that took place during gibbon evolution (Müller et al. 2003), 12 involved two gene-dense chromosomes, six rearrangements involved two chromosomes of intermediate gene-density and five involved two gene-poor chromosomes. 35 rearrangements took place between a gene-dense and an intermediate chromosome, 19 between gene-dense and gene-poor chromosomes and 18 between intermediate and gene-poor chromosomes (Note: when chromosome rearrangements were assigned to a putative last common ancestor of two or more gibbon species it was only counted once) (DOC 307 kb)

Supplementary Table 1

Classification of human chromosomes according to the gene density of each chromosome arm (NCBI build 33; http://www.ncbi.nlm.nih.gov) as gene-dense (15–27 genes/Mbp), gene-poor (0–12 genes/Mbp) or of intermediate gene density (12–15 genes/Mbp) and updated gene densities according to NCBI build 35.1. The color code refers to the probe labeling scheme used in FISH experiments illustrated in Figure 1A and Figure 2. Despite the fact that the overall number of bona fide genes has declined since, the relative gene density is still valid for most chromosomes (DOC 36 kb)

Supplementary Table 2

Statistical analysis of 3RRD evaluations obtained from 3D-FISH experiments (ARR=average relative radius; sem=standard error of the mean, P-values in red = statistically significant, P-values in blue = statistically not significant)(DOC 61 kb)

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Neusser, M., Schubel, V., Koch, A. et al. Evolutionarily conserved, cell type and species-specific higher order chromatin arrangements in interphase nuclei of primates. Chromosoma 116, 307–320 (2007). https://doi.org/10.1007/s00412-007-0099-3

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