PROMOTER ELEMENTS OF THE MOUSE COMPLEMENT C4 GENE CRITICAL FOR TRANSCRIPTION ACTIVATION AND START SITE LOCATION

We have explored the template and factor requirements for transcriptio n of the gene encoding the murine complement component C4, expressed p redominantly but not exclusively in liver and mononuclear phagocytes. Competition experiments in transcription assays with liver nuclear ext racts show that the regions upstream of the transcription initiation s ite are largely dispensable for obtaining basal levels of accurately i nitiated transcription. Activated transcription, however, depends on t hree upstream regulatory factors, two of which interact with target si tes seemingly related to NF-1 (region -112/-87) and USF (region -85/-6 4), respectively. A third upstream regulatory factor has been detected by the surprising finding that double-stranded oligomers covering seq uences proximal to the cap site (position -48 to -7) stimulate transcr iption from the C4 promoter specifically. Results of nucleotide deleti ons and site-directed mutations argue that the C4 initiator, that is, the most critical element for basal and accurate transcription of the gene, overlaps the cap site and extends into the transcribed sequences (-1 to +12). Immediately downstream of this region lies a last regula tory element (within the +5 to +43 boundaries) indispensable for high levels of transcription. These data assume wider interest because the C4 promoter does not contain TATA or CAAT boxes and does not feature a ny of the elements characteristic of the TATA less genes so far report ed.