The Bax inhibitor-1 gene is differentially regulated in adult testis and developing lung by two alternative TATA-less promoters

We identified Bar inhibitor-1, BI-1, as a developmentally regulated gene pr oduct in perinatal lung using suppressive subtractive hybridization. BI-1 i s a novel suppressor of apoptosis that was previously cloned as testis-enha nced gene transcript (TEGT). However, sequence analysis of lung BI-1 reveal ed unique nucleotides starting 29 bases upstream of the ATG initiation codo n and extending to the 5' end of lung-derived BI-1 cDNA compared to the ori ginal transcript from the testis, Cloning and sequencing of the upstream re gion of the BI-1 gene revealed that these unique sequences originated from two alternative first exons, located in tandem and separated by similar to 600 bases, Neither was preceded by a TATA box in the usual position, and Si nuclease mapping at each exon 1 revealed multiple transcription start poin ts with a major site being overlapped by a consensus initiator element. Pro moter activity from each region was documented by transient transfection an alysis in vitro using DNA sequences ligated to a reporter gene. The proxima l promoter, Pi, may exhibit cell type-specific differences in fibroblasts v ersus epithelia, whereas the distal promoter, P2, may exhibit species-speci fic differences in rat versus human cells. RT-PCR analysis for expression i n adult tissues using exon 1-specific 5' primers and common 3' primers reve aled that Pi is tissue-specific; P2 is ubiquitously active. The development al regulation of BI-1 in the late fetal and early postnatal lung is specifi c for P2, indicating that these two TATA-less promoters are differentially regulated in adult testis and developing lung. Since Bar inhibitor-1 functi ons as a suppressor of apoptosis, its expression could provide a survival a dvantage for select cell populations during the peak period of apoptosis th at occurs at birth. (C) 1999 Academic Press.