CD8 locus nuclear dynamics during thymocyte development.
Nuclear architecture and chromatin reorganization have recently been shown to orchestrate gene expression and act as key players in developmental pathways. To investigate how regulatory elements in the mouse CD8 gene locus are arranged in space and in relation to each other, three-dimensional fluorescence in situ hybridization and chromosome conformation capture techniques were employed to monitor the repositioning of the locus in relation to its subchromosomal territory and to identify long-range interactions between the different elements during development. Our data demonstrate that CD8 gene expression in murine lymphocytes is accompanied by the relocation of the locus outside its subchromosomal territory. Similar observations in the CD4 locus point to a rather general phenomenon during T cell development. Furthermore, we show that this relocation of the CD8 gene locus is associated with a clustering of regulatory elements forming a tight active chromatin hub in CD8-expressing cells. In contrast, in nonexpressing cells, the gene remains close to the main body of its chromosomal domain and the regulatory elements appear not to interact with each other.
Ktistaki
Eleni
E
Division of Molecular Immunology, Medical Research Council, National Institute for Medical Research, London, United Kingdom.
Garefalaki
Anna
A
Williams
Adam
A
Andrews
Simon R
SR
Bell
Donald M
DM
Foster
Katie E
KE
Spilianakis
Charalampos G
CG
Flavell
Richard A
RA
Kosyakova
Nadezda
N
Trifonov
Vladmir
V
Liehr
Thomas
T
Kioussis
Dimitris
D
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D016827:CD8 Antigens / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D002467:Cell Nucleus / Q000235:genetics*; D045584:Chromosome Positioning / Q000235:genetics; D015342:DNA Probes / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000276:immunology*; D021621:Imaging, Three-Dimensional; D017404:In Situ Hybridization, Fluorescence; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D017434:Protein Structure, Tertiary / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; C431698:CD8alpha antigen; C477867:CD8beta antigen; D015342:DNA Probes