Differing utilization of homologous transcription initiation sites of rat K and T kininogen genes under inflammation condition.

Two types of rat kininogen mRNAs exhibit marked differences in the regulation of their expressions. The two T kininogen (T) mRNAs considerably increase under acute inflammation conditions, although no such increase occurs in the high molecular weight and low molecular weight K kininogen (K) mRNAs encoded by the same gene. This investigation examines the sequences of the 5' portions of the K and the two T genes and analyzes transcription initiation sites and their utilization at differently regulated conditions of the K and T genes. The sequence analysis indicates that the K and the two T genes are extremely homologous at the 5' portions as well as the 5'-flanking regions of at least 1.0 kilobase pairs. The S1 nuclease and primer extension analyses show that both T and K mRNAs start with three sets of the homologous initiation sites, and the utilization of the two 3'-side initiation sites of the T genes markedly increases under inflammation conditions. In contrast, no such elevation is observed for the three initiation sites of the K gene. Thus, although the sequences involved as transcription initiation sites are extremely homologous, their utilizations in the expressions of the K and T genes are regulated differently under inflammation conditions.