title: Aberrant expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice.
abstract: The Th2 locus control region (LCR) has been shown to be a crucial cis-acting element for Th2 cytokine expression and Th2 cell differentiation. To study the role of Th2 LCR in ifng locus regulation, we examined the expression of IFN-γ in Th2 cells from Th2 LCR-deficient mice. We found IFN-γ to be aberrantly up-regulated. In addition, histone 3(H3)-acetylation and histone 3 lysine 4 (H3-K4)-methylation greatly increased at the ifng locus of the Th2 cells. GATA-3 and STAT6 bound to the ifng promoter in Th2 cells from the wild type but not from the Th2 LCR-deficient mice, and they directly repressed ifng expression in transient reporter assay. Moreover, ectopic expression of GATA-3 and STAT6-VT repressed the aberrant expression of the ifng gene and restored repressive chromatin state at the ifng locus in Th2 cells from Th2 LCR-deficient mice. These results suggest that expression of the ifng gene and chromatin remodeling of the ifng locus are under the control of a Th2 LCR-mediated Th2 differentiation program.
authors: Department of Life Science, Sogang University, Seoul 121-742, Republic of Korea.
authors: Soo Seok
authors: SS
authors: Hwang
authors: Kiwan
authors: K
authors: Kim
authors: Wonyong
authors: W
authors: Lee
authors: Gap Ryol
authors: GR
authors: Lee
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics*; D019901:Locus Control Region / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D050800:STAT6 Transcription Factor / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D002843:Chromatin; D050990:GATA3 Transcription Factor; D050800:STAT6 Transcription Factor; D007371:Interferon-gamma