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Evolutionarily conserved sequence elements that positively regulate IFN-γ small gamma expression in T cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 8/24/2004, Vol. 101 Issue 34, p12622-12627. 6p. - Publication Year :
- 2004
-
Abstract
- Our understanding of mechanisms by which the expression of IFN-γ is regulated is limited. Herein, we identify two evolutionarily conserved noncoding sequence elements (IFNgCNS1 and IFNg CNS2) located ≈5 kb upstream and ≈18 kb downstream of the initiation codon of the murine Ifng gene. When linked to the murine Ifng gene (-3.4 to +5.6 kb) and transiently transfected into EL-4 cells, these elements clearly enhanced IFN-γ expression in response to ionomycin and phorbol 12-myristate 13-acetate and weakly enhanced expression in response to T-bet. A DNase I hypersensitive site and extragenic transcripts at IFNgCNS2 correlated positively with the capacity of primary T cell subsets to produce IFN-γ. Transcriptionally favorable histone modifications in the Ifng promoter, intronic regions, IFNgCNS2, and, although less pronounced, IFNgCNSI increased as naïve T cells differentiated into IFN-γ-producing effector CD8+ and T helper (TH) 1 T cells, but not into TH2 T cells. Like IFN-γ expression, these histone modifications were T-bet-dependent in CD4+ cells, but not CD8+ T cells. These findings define two distal regulatory elements associated with T cell subset-specific IFN-γ expression. [ABSTRACT FROM AUTHOR]
- Subjects :
- *T cells
*CYTOKINES
*LYMPHOCYTES
*GENE expression
*TRANSCRIPTION factors
*HISTONES
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 101
- Issue :
- 34
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 14449146
- Full Text :
- https://doi.org/10.1073/pnas.0400849101