Autonomous and non-autonomous properties of small chromosome segments

The spatial arrangement of chromatin is linked to the regulation of nuclear processes. Onestriking aspect of nuclear organization is the spatial segregation of heterochromatin and euchromatin 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 and compared it to an orthologous region in the context of its 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: (i) gene-rich and SINE-rich euchromatin, (ii) gene-poor and LINE/LTR-rich heterochromatin and (iii) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show using 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 irrespectively of their chromosomal context, thus rendering this a chromosome segment autonomous property. Interactions with the nuclear lamina are also partially retained in the HAC but demonstrate less autonomy. Taken together, our results show that genomic segments autonomously fold and position themselves relative to other genomic parts, suggesting that the three major classes of chromatin constitute a blueprint for the overall nuclear architecture.