Fig. 3

Simplified model of radial chromosome and gene organisation in the cell nuclei. Upper left: In the cell nucleus, chromosomes composed of gene dense and gene poor bands are arranged in a zig-zag manner, with the gene poor regions (blue segments) close to the nuclear envelope, in a compact, generally not-transcribed, chromatin organisation. The gene dense regions (red segments) are located in a more internal position, with an open chromatin structure, that favour gene transcription. The interaction of cis-acting or trans-acting sequences, as well as the presence of specific regulatory factors consents gene activation. Upper right: a chromosomal translocation that involves regions normally positioned in different areas of the nucleus could determine an ectopic activation of translocated genes, on the basis of the new nuclear environment where they are repositioned. Bottom panel: Schematic representation of the distribution of FISH signals relative to the regions involved in the t(7;12) rearrangement. Left: Both copies of HLXB9 occupy a peripheral positioning, whereas both copies of ETV6 are localised towards the interior in the nucleus of normal cells. Right: The HLXB9 gene translocated on the der(12) is repositioned towards the nuclear interior, whereas the remaining portion of the ETV6 gene translocated on the der(7) is repositioned towards the nuclear periphery