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.
Expression of cell surface MHC class I:peptide complex requires coordinated expression of multiple genes such as MHC class I heavy chain, beta(2)-microglobulin (beta(2)m), 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, beta(2)m, 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.
Guo
Yong
Y
Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, 129 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.
Yang
Tianyu
T
Liu
Xingluo
X
Lu
Shengli
S
Wen
Jing
J
Durbin
Joan E
JE
Liu
Yang
Y
Zheng
Pan
P
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D026905:Amino Acid Transport Systems; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005095:Exoribonucleases; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology*; D020218:Response Elements; D029701:Saccharomyces cerevisiae Proteins; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D026905:Amino Acid Transport Systems; D029701:Saccharomyces cerevisiae Proteins; C429825:TAT2 protein, S cerevisiae; D007371:Interferon-gamma; D005095:Exoribonucleases