Distal Regions of the Human IFNG Locus Direct Cell Type-Specific Expression

被引:29
作者
Collins, Patrick L. [2 ]
Chang, Shaojing [4 ,5 ]
Henderson, Melodie [4 ,5 ]
Soutto, Mohammed [4 ,5 ]
Davis, Georgia M. [4 ,5 ]
McLoed, Allyson G. [4 ,5 ]
Townsend, Michael J.
Glimcher, Laurie H.
Mortlock, Douglas P. [3 ]
Aune, Thomas M. [1 ,2 ,4 ,5 ]
机构
[1] Vanderbilt Univ, Med Ctr, Div Rheumatol, Dept Med,Sch Med, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA
[4] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
ENCODING INTERFERON-GAMMA; KILLER DENDRITIC CELLS; CD8; T-CELLS; REGULATORY ELEMENTS; TRANSCRIPTION FACTOR; NK CELLS; LINEAGE COMMITMENT; GENE-EXPRESSION; CUTTING EDGE; BET;
D O I
10.4049/jimmunol.1000124
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Genes, such as IFNG, which are expressed in multiple cell lineages of the immune system, may employ a common set of regulatory elements to direct transcription in multiple cell types or individual regulatory elements to direct expression in individual cell lineages. By employing a bacterial artificial chromosome transgenic system, we demonstrate that IFNG employs unique regulatory elements to achieve lineage-specific transcriptional control. Specifically, a one 1-kb element 30 kb upstream of IFNG activates transcription in T cells and NKT cells but not in NK cells. This distal regulatory element is a Runx3 binding site in Th1 cells and is needed for RNA polymerase II recruitment to IFNG, but it is not absolutely required for histone acetylation of the IFNG locus. These results support a model whereby IFNG uses cis-regulatory elements with cell type-restricted function. The Journal of Immunology, 2010, 185: 1492-1501.
引用
收藏
页码:1492 / 1501
页数:10
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