Nuclear positioning,higher-order folding,and gene expression of Mmu15 sequences are refractory to chromosomal translocation |
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Authors: | Kathy J Snow Sarah M Wright Yong Woo Laura C Titus Kevin D Mills Lindsay S Shopland |
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Institution: | (1) Institute for Molecular Biophysics, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA;(2) Graduate School of Biomedical Sciences, University of Maine, Orono, ME, USA; |
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Abstract: | Nuclear localization influences the expression of certain genes. Chromosomal rearrangements can reposition genes in the nucleus
and thus could impact the expression of genes far from chromosomal breakpoints. However, the extent to which chromosomal rearrangements
influence nuclear organization and gene expression is poorly understood. We examined mouse progenitor B cell lymphomas with
a common translocation, der(12)t(12;15), which fuses a gene-rich region of mouse chromosome12 (Mmu12) with a gene-poor region
of mouse chromosome15 (Mmu15). We found that sequences 2.3 Mb proximal and 2.7 Mb distal to the der(12)t(12;15) breakpoint
had different nuclear positions measured relative to the nuclear radius. However, their positions were similar on unrearranged
chromosomes in the same tumor cells and normal progenitor B cells. In addition, higher-order chromatin folding marked by three-dimensional
gene clustering was not significantly altered for the 7 Mb of Mmu15 sequence distal to this translocation breakpoint. Translocation
also did not correspond to significant changes in gene expression in this region. Thus, any changes to Mmu15 structure and
function imposed by the der(12)t(12;15) translocation are constrained to sequences near (<2.5 Mb) the translocation junction.
These data contrast with those of certain other chromosomal rearrangements and suggest that significant changes to Mmu15 sequence
are structurally and functionally tolerated in the tumor cells examined. |
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