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Deletions of Chromosome 7q Affect Nuclear Organization and HLXB9Gene Expression in Hematological Disorders

1
Department of Biological, Geological and Environmental Sciences, University of Catania, via Androne 81, 95124 Catania CT, Italy
2
Genome Engineering and Maintenance Network, Institute of Environment, Health and Societies, Brunel University London, Kingston Lane UB8 3PH, UK
3
Department of Biological and Environmental Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield AL10 9AB, UK
4
Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP), Centro Ricerca Tettamanti, Pediatric Department, University of Milano-Bicocca, 20900 Monza, Italy
5
College of Health and Life Science, Brunel University London, Kingston Lane UB8 3PH, UK
*
Authors to whom correspondence should be addressed.
Cancers 2019, 11(4), 585; https://doi.org/10.3390/cancers11040585
Received: 12 March 2019 / Revised: 3 April 2019 / Accepted: 19 April 2019 / Published: 25 April 2019
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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. View Full-Text
Keywords: genome organization; radial positioning; chromosome deletion; HLXB9 gene; MNX1 gene; chromosome 7; leukemia genome organization; radial positioning; chromosome deletion; HLXB9 gene; MNX1 gene; chromosome 7; leukemia
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Federico, C.; Owoka, T.; Ragusa, D.; Sturiale, V.; Caponnetto, D.; Leotta, C.G.; Bruno, F.; Foster, H.A.; Rigamonti, S.; Giudici, G.; Cazzaniga, G.; Bridger, J.M.; Sisu, C.; Saccone, S.; Tosi, S. Deletions of Chromosome 7q Affect Nuclear Organization and HLXB9Gene Expression in Hematological Disorders. Cancers 2019, 11, 585.

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