RT Journal
A1 van de Werken, Harmen J.G.
A1 Haan, Josien C.
A1 Feodorova, Yana
A1 Bijos, Dominika
A1 Weuts, An
A1 Theunis, Koen
A1 Holwerda, Sjoerd J.B.
A1 Meuleman, Wouter
A1 Pagie, Ludo
A1 Thanisch, Katharina
A1 Kumar, Parveen
A1 Leonhardt, Heinrich
A1 Marynen, Peter
A1 van Steensel, Bas
A1 Voet, Thierry
A1 de Laat, Wouter
A1 Solovei, Irina
A1 Joffe, Boris
T1 Small chromosomal regions position themselves autonomously according to their chromatin class
JF Genome Research 
JO Genome Research 
YR 2017 
FD June 01 
VO 27 
IS 6 
SP 922 
OP 933 
DO 10.1101/gr.213751.116 
UL http://genome.cshlp.org/content/27/6/922.abstract 
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.