Microsomal GST-I: genomic organization, expression, and alternative splicing of the human gene

In this paper we report the genomic organization of the human microsomal GS T-I gene. This gene spans 18 kb, and contains seven exons. Sequences that e ncode the 155 amino acid open reading frame are present in Exons II, III, I V, the 5'-untranslated region is present in Exons Ia, Ib, Ic, Id, and II, a nd the 3'-untranslated region is present in Exon IV. Exons Ia, Ib, Ic, Id, and III are alternatively spliced to generate at least six different mGST-I transcripts. The results of EST and PCR analysis show that most mGST-I tra nscripts terminate within Exon Ib, and primer extension analysis shows thes e transcripts initiate at three major sites located at 79, 81, and 88 nucle otides upstream of the ATG initiation codon. Sequences surrounding the puta tive initiation sites are G-C rich, and several Sp1 consensus binding sites were identified. Northern analysis shows that the human GST-I gene is pref erentially expressed as a 1.0 kb transcript in liver, and in several other tissues. Finally, a comparison of the mGST-I and PIG12 sequences with those of FLAP, LTC4 synthase, mGST-II, and mGST-III suggests that these proteins are the related products of a dispersed microsomal GST gene superfamily. ( C) 1999 Elsevier Science B.V. All rights reserved.