Novel promoter I.8 and promoter usage in the CYP19 (aromatase) gene

Abstract

To date, 10 promoters were reported to regulate the expression of the human aromatase (CYP19) gene, giving rise to transcripts with an identical coding region but tissue-specific first exons comprising unique 5'-untranslated regions. We describe the identification and characterization of a new CYP19 exon I, designated exon I.8, in a 5'-rapid amplification of complementary DNA ends-generated library of human THP-1 monocytic cells. A construct containing exon I.8 and its 5'-flanking sequence was sufficient to drive transcription in THP-1 cells. This novel promoter was located approximately 2-kb upstream of promoter I.4 and approximately 75-kb upstream of the common splice junction. We detected several I.8-containing splice variants, 2 of which also contained a sequence from exon I.4. Analysis of human tissues revealed a unique pattern of promoter I.8 usage. The placenta contained the highest level of I.8-specific transcripts. This work underscores the complexity of the mechanisms that regulate normal and pathologic aromatase expression.