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International Immunology, Vol. 14, No. 2, 189-200, February 2002
© 2002 Japanese Society for Immunology

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-{gamma}-mediated activation of the transcription initiator

Yong Guo2, Tianyu Yang, Xingluo Liu, Shengli Lu, Jing Wen, Joan E. Durbin1, Yang Liu and Pan Zheng

Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA
1 Department of Pediatrics, Columbus Children's Hospital, Ohio State University, Columbus, OH 43205, USA
2 Present address: Hoechst Marion Rousse, Inc., CNS-Molecular Biology, Bridgewater, NJ 08807, USA

Correspondence to: P. Zheng; E-mail: zheng-1{at}medctr.osu.edu

Expression of cell surface MHC class I:peptide complex requires coordinated expression of multiple genes such as MHC class I heavy chain, ß2-microglobulin (ß2m), 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-{gamma}. While the cis elements involved in transcription of the MHC class I heavy chain, ß2m, 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-{gamma}, such as {gamma}-activation site and IFN response factor binding element (IRFE), only the IRFE is required for IFN-{gamma} 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.

Keywords: antigen presentation genes, IFN-{gamma} activation, transporters associated with antigen-processing-2, transcriptional regulation

Transmitting editor: R. A. Flavell


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