Small chromosomal regions position themselves autonomously according to their chromatin class

Harmen J G van de Werken, Josien C Haan, Yana Feodorova, Dominika Bijos, An Weuts, Koen Theunis, Sjoerd J B Holwerda, Wouter Meuleman, Ludo Pagie, Katharina Thanisch, Parveen Kumar, Heinrich Leonhardt, Peter Marynen, Bas van Steensel, Thierry Voet, Wouter de Laat, Irina Solovei, Boris Joffe

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)922-933
Aantal pagina's12
TijdschriftGenome Research
Volume27
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - jun 2017

Vingerafdruk

Duik in de onderzoeksthema's van 'Small chromosomal regions position themselves autonomously according to their chromatin class'. Samen vormen ze een unieke vingerafdruk.

Citeer dit