期刊
GENES AND IMMUNITY
卷 8, 期 1, 页码 35-43出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gene.6364349
关键词
gene conformation; CD4+T helper cell subsets; matrix attachment regions; chromosome conformation capture; DNA oligonucleotide array
资金
- NIAID NIH HHS [AI44924] Funding Source: Medline
- NIAMS NIH HHS [AR07491] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R56AI044924, R01AI044924] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [T32AR007491] Funding Source: NIH RePORTER
Cytokine genes undergo progressive changes in chromatin organization when naive CD4+ T helper (Th) cells differentiate into committed Th1 and Th2 lineages. Here, we analyzed nuclear matrix attachment regions (MARs) in the Ifng gene by DNA array technique in unactivated and activated CD4+ Th cells. This approach was combined with analysis of spatial organization of the Ifng gene by chromosome conformation capture approach to assess the relationship between the gene conformation and matrix attachment organization in functionally different cell subsets. We report that the Ifng gene in unactivated cells displays a linear conformation, but in T-cell receptor-activated cells, it adopts a loop conformation. The selective MARs support the spatial gene organization and characteristically define the Ifng gene in functionally different cell subsets. The pattern of interaction of the Ifng gene with the nuclear matrix dynamically changes in a lineage-specific manner in parallel with the changes in Ifng gene conformation. The data suggest that such structural dynamics provide the means for transcriptional regulation of the Ifng gene in the course of activation and differentiation of CD4+ Th cells.
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