Deletions of chromosome 7q affect nuclear organisation and HLXB9 gene expression in haematological disorders

Abstract

The radial spatial positioning of individual gene loci within interphase nuclei has been associated with up- and downregulation of their expression. In cancer, the genome organisation may become disturbed due to chromosomal abnormalities such as translocations or deletions, resulting in the repositioning of genes and alteration of gene expression with oncogenic consequences. In this study, we analysed the nuclear repositioning of HLXB9 (also called MNX1), mapping at 7q36.3, in haematological patients carrying interstitial deletions of 7q of various extents, with distal breakpoint in 7q36. We observed that HLXB9 remains at the nuclear periphery or is repositioned towards the nuclear interior depending on the compositional properties of the chromosomal regions involved in the rearrangement. For instance, a proximal breakpoint leading the GC-poor band 7q21 near 7q36 would bring HLXB9 to the nuclear periphery, whereas breakpoints that join the GC-rich band 7q22 to 7q36 would bring HLXB9 to the nuclear interior. This nuclear repositioning is associated with transcriptional changes, with HLXB9 in the nuclear interior becoming upregulated. Here we report an in cis rearrangement involving one single chromosome altering gene behaviour. Furthermore, we propose a mechanistic model for chromatin reorganisation that affects gene expression via the influences of new chromatin neighbourhoods.