Small chromosomal regions position themselves autonomously according to their chromatin class.
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.
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.
Harmen J G
0000-0002-9794-1477
HJG
van de Werken
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
Josien C
JC
Haan
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Yana
Y
Feodorova
Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Dominika
D
Bijos
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
An
A
Weuts
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
Koen
K
Theunis
Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
Sjoerd J B
SJB
Holwerda
Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Wouter
0000-0002-1196-5401
W
Meuleman
Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Ludo
L
Pagie
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Katharina
K
Thanisch
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
Parveen
P
Kumar
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Heinrich
H
Leonhardt
Human Genome Laboratory, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
Peter
P
Marynen
Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Bas
B
van Steensel
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium.
Thierry
T
Voet
Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands.
Wouter
W
de Laat
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Irina
I
Solovei
Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany.
Boris
B
Joffe
D000818:Animals; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D022222:Chromosomes, Artificial, Human / Q000378:metabolism* / Q000648:ultrastructure; D022041:Euchromatin / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D061251:Primary Cell Culture; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure
D022041:Euchromatin; D006570:Heterochromatin