Cutting edge: distal regulatory elements are required to achieve selective expression of IFN-gamma in Th1/Tc1 effector cells.
Using a transgenic approach, we analyzed the contribution of introns located within the IFN-gamma gene and distal regulatory regions to IFN-gamma gene expression. Intron 1 and 3 from the IFN-gamma gene displayed strong enhancer activity. This activity appeared to be dependent upon integration into the genome but resulted in a loss of Th1 selectivity. We also found that distal regulatory elements are not required for high level expression of the human IFN-gamma gene, but rather for cell lineage-specific expression. An 8.6-kb human IFN-gamma transgene was sufficient to yield high level expression but a 191-kb IFN-gamma transgene with approximately 90 kb of flanking 5' and 3' sequence was necessary to achieve both high level and Th1 selective expression of human IFN-gamma.
Soutto
Mohammed
M
Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Zhou
Weisong
W
Aune
Thomas M
TM
D000818:Animals; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004742:Enhancer Elements, Genetic / Q000276:immunology / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics*; D007438:Introns / Q000276:immunology / Q000502:physiology; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection
D007371:Interferon-gamma