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Genome Res. 2017 Jun;27(6):922-933. doi: 10.1101/gr.213751.116. Epub 2017 Mar 24.

Small chromosomal regions position themselves autonomously according to their chromatin class.

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Cancer Computational Biology Center, Erasmus MC Cancer Institute & Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands.
Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Human Genome Laboratory, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.


The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes.

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