Spatial genome organization during T-cell differentiationKim S.H.a · McQueen P.G.b · Lichtman M.K.c · Shevach E.M.c · Parada L.A.a · Misteli T.a
aNational Cancer Institute, NIH; bMathematical and Statistical Laboratory, DCB, CIT, NIH, and cNational Institute of Allergy and Infectious Diseases, Laboratory of Immunology, Bethesda, MD (USA)
The spatial organization of genomes within the mammalian cell nucleus is non-random. The functional relevance of spatial genome organization might be in influencing gene expression programs as cells undergo changes during development and differentiation. To gain insight into the plasticity of genomes in space and time and to correlate the activity of specific genes with their nuclear position, we systematically analyzed the spatial genome organization in differentiating mouse T-cells. We find significant global reorganization of centromeres, chromosomes and gene loci during the differentiation process. Centromeres were repositioned from a preferentially internal distribution in undifferentiated cells to a preferentially peripheral position in differentiated CD4+ and CD8+ cells. Chromosome 6, containing the differentially expressed T-cell markers CD4 and CD8, underwent differential changes in position depending on whether cells differentiated into CD4+ or CD8+ thymocytes. Similarly, the two marker loci CD4 and CD8 showed distinct behavior in their position relative to the chromosome 6 centromere at various stages of differentiation. Our results demonstrate that significant spatial genome reorganization occurs during differentiation and indicate that the relationship between dynamic genome topology and single gene regulation is highly complex.
Request reprints from: Dr. Tom Misteli, National Cancer Institute, NIH
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S.H.K. and M.K.L. are HHMI-NIH Research Scholars. T.M. is a Keith R. Porter Fellow.
Received 1 October 2003;
manuscript accepted 17 October 2003.
Number of Print Pages : 10
Number of Figures : 6, Number of Tables : 0, Number of References : 52
Cytogenetic and Genome Research
Formerly ‘Cytogenetics and Cell Genetics’
Vol. 105, No. 2-4, Year 2004 (Cover Date: 2004)
Journal Editor: H.P. Klinger, Bronx, N.Y.; M. Schmid, Würzburg
ISSN: 1424–8581 (print), 1424–859X (Online)
For additional information: http://www.karger.com/journals/cgr