Nuclear positioning, higher-order folding, and gene expression of Mmu15 sequences are refractory to chromosomal...

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 chromosome 12 (Mmu 12) with a gene-poor region of mouse chromosome 15 (Mmu 15). 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 Mmu 15 sequence distal to this translocation breakpoint. Translocation also did not correspond to significant changes in gene expression in this region. Thus, any changes to Mmu 15 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 Mmu 15 sequence are structurally and functionally tolerated in the tumor cells examined.