IDENTIFICATION OF SEQUENCES RESPONSIBLE FOR POSITIVE AND NEGATIVE REGULATION BY E1A IN THE PROMOTER OF H-2KBM1 CLASS-I MHC GENE

The mechanism of transcriptional regulation of the H-2K(bm1) major histocompatibility complex (MHC) class I gene by adenovirus type 12 E1A (Ad12-E1A) was studied in transfected rat embryonal fibroblasts. Results of long-term expression of the chloramphenicol acetyl transferase CAT) gene placed under the control of the 5'-flanking region of the mouse MHC class I gene, H-2K(bm1), and the results of nuclear run-on transcription assays, yield evidence for both positive and negative regulation of H-2K(bm1) by E1A gene product Deletion studies in the H-2K(bm1) promoter region revealed that a proximal 58 bp upstream sequence (-194 to -136, relative to the cap site) and a distal 316 bp sequence (-1837 to -1521) respectively contribute to positive and negative regulation mediated by the E1A gene product. Both regulatory elements of MHC class I gene promoter region are reponsible for the differential expression of the H-2K(bm1) gene in Ad12 transformed cells. A nuclear factor binding to the negative element has been detected only in extracts derived from cells expressing Ad12-E1A.