Identification and characterization of two CD40-inducible enhancers in themouse TRAF1 gene locus

We have shown that CD40 engagement induces TRAF1 gene expression in B lymph ocytes. Here we report that CD40-dependent TRAF1 gene transcription in muri ne B cells is controlled by two enhancer regions. One region is located app roximately 2 kb upstream of the transcription start site and the other lies in the intron between exons 5 and 6. The upstream enhancer contains a sing le NF-kappaB site in addition to sites that bind constitutive transcription factors. Mutation of this NF-kappaB site completely abrogates CD40-driven TRAF1 transcription. The intronic enhancer contains two sites that strongly bind the CD40-inducible factors NF-kappaB and AP-1. Simultaneous mutation of the AP-1 site and of the NF-kappaB site abolishes transcription driven b y this enhancer. When cloned together into reporter constructs, the two TRA F1 enhancers do not synergize, suggesting that each enhancer may separately participate in the induction of TRAF1 transcription in B cells following C D40 activation. (C) 2001 Elsevier Science Ltd. All rights reserved.