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-
-mediated activation of the transcription initiator
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-
. 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-
, such as
-activation site and IFN response factor binding element (IRFE), only the IRFE is required for IFN-
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-
activation, transporters associated with antigen-processing-2, transcriptional regulation
Transmitting editor: R. A. Flavell
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