are spliced onto the coding region during transcription to create diverse GR mRNAs. The promoter, while spliced onto the mRNA, does not alter the translational phase by which mRNA is “translated” into the amino acid sequence that defines the protein product. The alternate exon 1 sequences are unlikely to alter the amino acid sequence of the GR protein; there is an “stop” codon present immediately 5' to the translation initiation site in exon 2, common to all the mRNA variants. Hence, only the coding region is actually translated into protein. Of the alternate exon 1 sequences identified, four correspond to exon 1 sequences previously identified in mouse, exons 11,15, 19, and 110 84,85 Most alternative exons are located in a 3-kb CpG island upstream of exon 2 that exhibits substantial promoter activity in transfected cells (Figure 2). Ribonuclease protection assays demonstrate significant levels of six alternative exon 1 sequences in vivo in the rat, with differential expression in the liver, hippocampus, and thymus presumably reflecting tissue-specific differences in promoter activity. The different promoters respond to different signals, which forms the basis for tissue-specific laterations in gene expression. Simply put, it is the process by which environmental or hormonal signals can
