University of Hertfordshire

Documents

  • Concetta Federico
  • Temitayo Owoka
  • Denise Ragusa
  • Valentina Sturiale
  • Domenica Caponnetto
  • Claudia Giovanna Leotta
  • Francesca Bruno
  • Helen Foster
  • Silvia Rigamonti
  • Giovanni Giudici
  • Giovanni Cazzaniga
  • Joanna Bridger
  • Cristina Sisu
  • Salvatore Saccone
  • Sabrina Tosi
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Original languageEnglish
Article number585
Number of pages19
JournalCancers
Journal publication date25 Apr 2019
Volume11
Issue4
DOIs
Publication statusPublished - 25 Apr 2019

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 organization 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 analyzed the nuclear repositioning of HLXB9 (also called MNX1), mapping at 7q36.3, in patients with hematological disorders carrying interstitial deletions of 7q of various extents, with a distal breakpoint in 7q36. We observed that HLXB9 remains at the nuclear periphery, or is repositioned towards the nuclear interior, depending upon the compositional properties of the chromosomal regions involved in the rearrangement. For instance, a proximal breakpoint leading the guanine-cytosine (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 behavior. Furthermore, we propose a mechanistic model for chromatin reorganization that affects gene expression via the influences of new chromatin neighborhoods.

Notes

© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

ID: 16632635