Constitutive Fas ligand gene transcription in Sertoli cells is regulated by Sp1

被引:63
作者
McClure, RF
Heppelmann, CJ
Paya, CV
机构
[1] Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Dept Pathol, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Dept Lab Med, Rochester, MN 55905 USA
关键词
D O I
10.1074/jbc.274.12.7756
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcriptional regulation of the Fas ligand (FasL) gene in Sertoli cells was investigated, as these cells are known to have constitutive expression of FasL and hence maintain an "immune privileged" environment within the testicle, Using the Sertoli cell line TM4, it was demonstrated that a gene segment of the 5'-untranslated region located between -318 and -237 relative to the translation start site is required for constitutive Fast transcription. Deletion and mutation analysis demonstrate that an Sp1 rather than an NFAT or NFKB-like DNA binding motif present within this region is necessary and sufficient for constitutive Fast gene transcription. Nuclear extracts of Sertoli cells contain Sp1 and Sp3 that specifically binds to the Sp1 motif present in the Fast gene, and overexpression of Sp1 but not Sp3 leads to a further increase of transcription from the Fast promoter-enhancer region. The data presented demonstrates that constitutive Fast gene transcription in Sertoli cells is regulated by Sp1. In addition, it is shown that basal Fast expression in Jurkat T cells is also controlled by Sp1 and this is in contrast to induced Fast expression, which is NFAT-dependent.
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页码:7756 / 7762
页数:7
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