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  • Original Article
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Selective matrix attachment regions in T helper cell subsets support loop conformation in the Ifng gene

Abstract

Cytokine genes undergo progressive changes in chromatin organization when naïve 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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Acknowledgements

We thank Drs Alan Hair and Sergey Razin for critical reading of the paper, Dr Igor Orlovski for help in designing the DNA array, Dr Iryna Pirozshkova and Ms Lena Prochnow for carrying out some of the hybridization experiments. We also thank Dr George Stricklin for his continued support and discussions. This work was supported by NIH Grants AI44924 and AR07491, USA, and Fondation de France, Grant 032145.

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Correspondence to E R Eivazova.

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Eivazova, E., Vassetzky, Y. & Aune, T. Selective matrix attachment regions in T helper cell subsets support loop conformation in the Ifng gene. Genes Immun 8, 35–43 (2007). https://doi.org/10.1038/sj.gene.6364349

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