MODULATION OF APRT TRANSCRIPTION BY ALTERING SPACING BETWEEN CIS-REGULATORY ELEMENTS

Three regulatory regions on the promoter of CHO adenine phosphoribosyl transferase gene (APRT) were identified. Spacing constraints between t hese regions were analyzed. With normal spacing, region II (-33 to $19 ), which separates regions I (-101 to -53) and III (+56 to +85), is cr itical for APRT transcription. However, when regions I and III are art ificially placed in proximity to each other (region II deleted), they are able to drive transcription as efficiently as the wild-type APRT p romoter. Neither region I nor III alone is sufficient for efficient tr anscription. As the spacing between the two regions increases, the tra nscription decreases. Region I may activate transcription in two ways: through a stringent sequence-specific manner (as in the transcription mediated by regions I and III) and through a manner with relaxed I re quirement for sequence specificity (as in the transcription from the w ild-type APRT promoter).