PMID- 28341771 OWN - NLM STAT- MEDLINE DCOM- 20180309 LR - 20220129 IS - 1549-5469 (Electronic) IS - 1088-9051 (Print) IS - 1088-9051 (Linking) VI - 27 IP - 6 DP - 2017 Jun TI - Small chromosomal regions position themselves autonomously according to their chromatin class. PG - 922-933 LID - 10.1101/gr.213751.116 [doi] AB - 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. CI - (c) 2017 van de Werken et al.; Published by Cold Spring Harbor Laboratory Press. FAU - van de Werken, Harmen J G AU - van de Werken HJG AUID- ORCID: 0000-0002-9794-1477 AD - Cancer Computational Biology Center, Erasmus MC Cancer Institute & Department of Urology, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 CN, Rotterdam, The Netherlands. AD - Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands. FAU - Haan, Josien C AU - Haan JC AD - Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium. FAU - Feodorova, Yana AU - Feodorova Y AD - Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany. FAU - Bijos, Dominika AU - Bijos D AD - Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. FAU - Weuts, An AU - Weuts A AD - Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium. FAU - Theunis, Koen AU - Theunis K AD - Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium. FAU - Holwerda, Sjoerd J B AU - Holwerda SJB AD - Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands. FAU - Meuleman, Wouter AU - Meuleman W AUID- ORCID: 0000-0002-1196-5401 AD - Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. FAU - Pagie, Ludo AU - Pagie L AD - Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. FAU - Thanisch, Katharina AU - Thanisch K AD - Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany. FAU - Kumar, Parveen AU - Kumar P AD - Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium. FAU - Leonhardt, Heinrich AU - Leonhardt H AD - Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany. FAU - Marynen, Peter AU - Marynen P AD - Human Genome Laboratory, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium. FAU - van Steensel, Bas AU - van Steensel B AD - Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. FAU - Voet, Thierry AU - Voet T AD - Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, 3000, Belgium. FAU - de Laat, Wouter AU - de Laat W AD - Hubrecht Institute-KNAW & University Medical Center Utrecht, 3584 CT Utrecht, The Netherlands. FAU - Solovei, Irina AU - Solovei I AD - Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany. FAU - Joffe, Boris AU - Joffe B AD - Department of Biology II, Ludwig Maximilians University Munich, 82152 Planegg-Martinsried, Germany. LA - eng GR - 293662/ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170324 PL - United States TA - Genome Res JT - Genome research JID - 9518021 RN - 0 (Euchromatin) RN - 0 (Heterochromatin) SB - IM MH - Animals MH - Cell Line, Transformed MH - Cell Nucleus/*genetics/metabolism/ultrastructure MH - Chromosomes, Artificial, Human/*metabolism/ultrastructure MH - Euchromatin/classification/*metabolism/ultrastructure MH - Fibroblasts/*metabolism/ultrastructure MH - Gene Expression Profiling MH - Gene Expression Regulation MH - Heterochromatin/classification/*metabolism/ultrastructure MH - Humans MH - In Situ Hybridization, Fluorescence MH - Mice MH - Primary Cell Culture MH - Retina/*metabolism/ultrastructure PMC - PMC5453326 EDAT- 2017/03/28 06:00 MHDA- 2018/03/10 06:00 PMCR- 2017/12/01 CRDT- 2017/03/26 06:00 PHST- 2016/08/01 00:00 [received] PHST- 2017/03/22 00:00 [accepted] PHST- 2017/03/28 06:00 [pubmed] PHST- 2018/03/10 06:00 [medline] PHST- 2017/03/26 06:00 [entrez] PHST- 2017/12/01 00:00 [pmc-release] AID - gr.213751.116 [pii] AID - 10.1101/gr.213751.116 [doi] PST - ppublish SO - Genome Res. 2017 Jun;27(6):922-933. doi: 10.1101/gr.213751.116. Epub 2017 Mar 24.