Isolation of a B-cell-specific promoter for the human class II transactivator

被引:74
作者
Lennon, AM
Ottone, C
Rigaud, G
Deaven, LL
Longmire, J
Fellous, M
Bono, R
AlcaideLoridan, C
机构
[1] INST PASTEUR,INSERM,U276,UNITE IMMUNOGENET HUMAINE,F-75724 PARIS 15,FRANCE
[2] INST PASTEUR,INSERM,U276,UNITE IMMUNOGENET,F-75724 PARIS 15,FRANCE
[3] LOS ALAMOS NATL LAB,CTR HUMAN GENOME STUDIES,LOS ALAMOS,NM 87545
[4] UNIV CHILE,FAC CIENCIAS,DEPT BIOL,SANTIAGO,CHILE
关键词
D O I
10.1007/s002510050202
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The class II transactivator (CIITA) is essential for the expression of major histocompatibility complex (MHC) class II antigens. The tissular patterns of CIITA and MHC class II gene expression are tightly correlated: CIITA mRNA is highly expressed in B cells, and is induced by interferon gamma (IFN-gamma) in macrophage and epithelial cell lines. We first isolated two overlapping cosmids encoding human CIITA which, when co-transfected, are able to restore MHC class II expression in a B-lymphoblastoid cell line (B-LCL) defective for CIITA. Subsequently, a 1.8 kilobase (kb) fragment of the CIITA promoter was isolated and sequenced. A motif presenting a strong similarity to an initiator was detected, as well as putative binding sites for Spl, GATA-2, LyF-1, ets-1, AP1, and MZF1 transcription factors, and two GAS motifs. When introduced in front of a luciferase reporter gene, this promoter is able to direct a high luciferase activity in a human B-LCL. In contrast, luciferase expression was not stimulated after IFN-gamma treatment when the construct was transfected in macrophage or in epithelial cell lines. However, an induction of the human CIITA gene was observed in mouse macrophage and fibrosarcoma cell lines, when the cells were transfected with a cosmid containing the human CIITA gene, but lacking the 1.8 kb promoter described above. Taken together, these data suggest the existence of an intragenic promoter driving an IFN-gamma-inducible expression of CIITA.
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页码:266 / 273
页数:8
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