TGF beta-inducible early gene (TIEG) and early growth response alpha (EGR alpha) are putative transcription factors based on homology to known zinc finger proteins SP1, EGR1, BTEB, and Wilm tumor. Here we report that TIEG and EGR alpha are expressed from alternative promoters of the same gene. The TIEG/EGR alpha gene spans 8 kb and contains five exons. Use of alternative first exons results in TIEG having 12 unique amino acids on its N-terminus. Computer analysis of the 5' upstream regions of either TIEG (exon 1a) or EGR alpha (exon 1b) does not identify a TATA box or initiator sequence but shows consensus sequence similarities to binding sites for several transcription factors including SP1, JunB, and aromatic hydrocarbon/receptor-ligand complexes. Analysis of constructs containing 5'-flanking regions show that both the TIEG and the EGR alpha promoters have significant activity in human fetal osteoblast cells. Northern analysis of mRNA from various human tissues and several cell lines reveals that TIEG is the predominant transcript produced and regulated by growth factors from the TIEG/EGR alpha gene. (C) 1998 Academic Press