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.
|Original language||English (US)|
|Number of pages||11|
|State||Published - Feb 2011|
Bibliographical noteFunding Information:
Acknowledgments We thank Drs. Mary Ann Handel, Anne Peaston, Casey Fox, and Laura Reinholdt for critical reading of this manuscript. We also thank the contributions of The Jackson Laboratory Imaging Sciences, Flow Cytometry, Gene Expression, and Computational Biology Resource services, and Dr. David Serreze for protocols and reagents to isolate primary progenitor B cells. This work was supported by grants from the National Science Foundation (MCB 0817787 (LSS), EPScOR 0132384, and IGERT 0221625), the National Institutes of Health National Center for Research Resources (INBRE 5P20RR016463-08, P20 RR018789) and National Cancer Institute (R01 CA115666 (KDM), CA034196), and the Maine Cancer Foundation (LSS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NSF or NIH. Experiments conducted in this report comply with current laws of the United States of America. The authors declare that there are no financial conflicts of interest associated with this work.
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