Organization and functional analysis of the mouse transporter associated with antigen processing 2 promoter

In accordance with the key role of MHC class I molecules in the adaptive im mune response against viruses, they are expressed by most cells, and their expression can be enhanced by cytokines. The assembly and cell surface expr ession of class I complexes depend on a continuous peptide supply. The pept ides are generated mainly by the proteasome and are transported to the endo plasmic reticulum by a peptide transport pump consisting of two subunits, T AP1 and TAP2, The proteasome low molecular weight polypeptide (2 and 7), as well as TAP (1 and 2) genes, are coordinately regulated and are induced by IFNs, Despite this coordinate regulation, examination of tumors shows that these genes can be discordantly down-regulated, In pursuing a molecular ex planation for these observations, we have characterized the mouse TAP2 prom oter region and 5'-flanking sequence, We show that the 5' untranslated regi ons of TAP2 genes have a characteristic genomic organization that is conser ved in both the mouse and the human, The mouse TAP2 promoter belongs to a c lass of promoters that lack TATA bares hut contain a MED1 (multiple start s ite element downstream) sequence. Accordingly, transcription is initiated f rom multiple sites within a 100-nucleotide window, An IFN regulatory factor 1 (IRF1)/IRF2 binding site is located in this region and is involved in bo th basal and IRF1-induced TAP2 promoter activity, The implication of the ex tensive differences found among the promoters of class I heavy chain, low m olecular weight polypeptide, and TAP genes, all encoding proteins involved in Ag presentation, is discussed.