Cis elements for transporter associated with antigen-processing-2 transcription: two new promoters and an essential role of the IFN response factor binding element in IFN-γ-mediated activation of the transcription initiator

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Abstract
Expression of cell surface MHC class I:peptide complex requires coordinated expression of multiple genes such as MHC class I heavy chain, β2-microglobulin (β2m), transporters associated with antigen-processing (TAP)-1 and TAP-2, and proteosomal components low-molecular weight polypeptide (LMP)-2 and LMP-7. All of these genes are expressed at defined and distinct levels in normal tissues, and are inducible by IFN-γ. While the cis elements involved in transcription of the MHC class I heavy chain, β2m, TAP-1 and LMP-2 have been analyzed extensively, those for TAP-2 and LMP-7 have not been well studied. Here we systematically analyzed the cis elements for TAP-2 transcription. We found at least two independent elements that are sufficient to activate transcription of a reporter gene. One (hereby called TAP-2 P1) is located 5′ to the TAP-2 exon 1, while the other (hereby called TAP-2 P2) is a transcription initiator residing in intron 1. Analysis of the 5′ sequence of TAP-2 mRNA indicates that both promoters are active. Moreover, while the TAP-2 promoter region contains cis elements that can mediate TAP-2 induction by IFN-γ, such as γ-activation site and IFN response factor binding element (IRFE), only the IRFE is required for IFN-γ induction of TAP-2 promoter in vitro. The IRFE appears to work as an enhancer for the initiator (P2). Together with another promoter recently identified by others, TAP-2 therefore has three independent promoters that can be differentially regulated.