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

Genomics. 1999 Apr 15;57(2):201-8. doi: 10.1006/geno.1999.5761.

Abstract

We identified Bax inhibitor-1, BI-1, as a developmentally regulated gene product in perinatal lung using suppressive subtractive hybridization. BI-1 is a novel suppressor of apoptosis that was previously cloned as testis-enhanced gene transcript (TEGT). However, sequence analysis of lung BI-1 revealed unique nucleotides starting 29 bases upstream of the ATG initiation codon and extending to the 5' end of lung-derived BI-1 cDNA compared to the original transcript from the testis. Cloning and sequencing of the upstream region of the BI-1 gene revealed that these unique sequences originated from two alternative first exons, located in tandem and separated by approximately 600 bases. Neither was preceded by a TATA box in the usual position, and S1 nuclease mapping at each exon 1 revealed multiple transcription start points with a major site being overlapped by a consensus initiator element. Promoter activity from each region was documented by transient transfection analysis in vitro using DNA sequences ligated to a reporter gene. The proximal promoter, P1, may exhibit cell type-specific differences in fibroblasts versus epithelia, whereas the distal promoter, P2, may exhibit species-specific differences in rat versus human cells. RT-PCR analysis for expression in adult tissues using exon 1-specific 5' primers and common 3' primers revealed that P1 is tissue-specific; P2 is ubiquitously active. The developmental regulation of BI-1 in the late fetal and early postnatal lung is specific for P2, indicating that these two TATA-less promoters are differentially regulated in adult testis and developing lung. Since Bax inhibitor-1 functions as a suppressor of apoptosis, its expression could provide a survival advantage for select cell populations during the peak period of apoptosis that occurs at birth.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Blotting, Northern
  • Cell Line
  • DNA / chemistry
  • DNA / genetics
  • DNA, Complementary / genetics
  • Fetus / metabolism
  • Gene Expression Regulation, Developmental
  • HeLa Cells
  • Humans
  • Lung / embryology
  • Lung / growth & development
  • Lung / metabolism*
  • Male
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Proteins*
  • RNA / genetics
  • RNA / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • TATA Box
  • Testis / metabolism*
  • Tissue Distribution
  • Transcription, Genetic

Substances

  • Apoptosis Regulatory Proteins
  • DNA, Complementary
  • Membrane Proteins
  • Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • TMBIM6 protein, human
  • Tmbim6 protein, rat
  • RNA
  • DNA

Associated data

  • GENBANK/AF118564