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

• Published in: Genes and immunity Vol. 8; no. 1; pp. 35 - 43
• Main Authors: Eivazova, E R, Vassetzky, Y S, Aune, T M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.01.2007
• Subjects: Animals; Biophysics; CD4 antigen; CD4 lymphocytes; Cell differentiation; Chromatin; Chromosome Structures - metabolism; Chromosomes; Chromosomes, Mammalian - chemistry; Conformation; Cytokines; DNA methylation; DNA microarrays; Gene expression; Gene Expression Regulation; Gene loci; Gene regulation; Genetic aspects; Genetic Techniques; Genomes; Helper cells; Interferon-gamma - genetics; Lithium Compounds - pharmacology; Lymphocyte Activation - genetics; Lymphocytes; Lymphocytes T; Matrix attachment regions; Matrix Attachment Regions - drug effects; Medicine; Mice; Mice, Inbred C57BL; Nuclear Matrix - metabolism; Oligonucleotide Array Sequence Analysis; Physiological aspects; Physiology; Specific Pathogen-Free Organisms; Spleen - cytology; T cell receptors; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - metabolism; Transcription; United States; United States > US; Nashville Tennessee
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364349

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.