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

• Published in: Chromosoma Vol. 120; no. 1; pp. 61 - 71
• Main Authors: Snow, Kathy J, Wright, Sarah M, Woo, Yong, Titus, Laura C, Mills, Kevin D, Shopland, Lindsay S
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-02-2011; Springer-Verlag; Springer Nature B.V
• Subjects: Animal Genetics and Genomics; Animals; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Line, Tumor; Chromatin - genetics; Chromatin - metabolism; Chromosomes, Mammalian - genetics; Chromosomes, Mammalian - metabolism; Developmental Biology; Eukaryotic Microbiology; Gene Expression Regulation, Neoplastic; Human Genetics; Life Sciences; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - metabolism; Mice; Research Article; Translocation, Genetic; Nuclear Position; Nuclear Periphery; Gene Desert; Translocation Breakpoint; Apply Spectral Image
• ISSN: 0009-5915; 1432-0886
• DOI: 10.1007/s00412-010-0290-9

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.