J Steroid Biochem Mol Biol 2012 Nov 01;1323-5:247-55. doi: 10.1016/j.jsbmb.2012.05.007.

Brain-specific promoter/exon I.f of the cyp19a1 (aromatase) gene in Xenopus laevis.

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Aromatase, encoded by the cyp19a1 gene, is the key enzyme for estrogen biosynthesis. Exon I.f of aromatase transcripts in the Xenopus brain is driven in a brain-specific manner. In this study, we cloned brain aromatase with a 5'-end of various lengths by 5'-RACE and detected the expression pattern of the aromatase mRNA. In Xenopus at the larval stage, the brain aromatase mRNA expression was five-fold higher than those in the gonad and liver, and was upregulated from stage 42 to stage 50. After isolating the brain-specific promoter I.f, which was located ∼6.5 kb upstream from gonad-specific exon PII, we observed this promoter in a potential cis-elements for several transcriptional factors, such as Oct-1, c-Myc, the GATA gene family, C/EBPalpha, Sox5, p300, XFD-1, AP1, the STAT gene family, FOXD3, and the Smad gene family. In addition, the core promoter elements of two initiators and an atypical TATA box were found around the 5'-RACE products. In the 5'-flanking region of exon I.f, the binding sites for nuclear extracts suggested that the followings are important: the STAT gene family, a 38-bp conserved region among five species, FOXD3, and the Smad gene family within the region 200 bp upstream from the transcription initiation site. Real-time RT-PCR analysis showed that the foxd3, smad2 and smad4.1/4.2 mRNAs are specifically expressed in the brain. Furthermore, the expression change of foxd3, which has been reported as a repressor, indicated that expression decreased to stage 50 from stage 42, contrary to that of aromatase mRNA. These results may imply that foxd3 expression decreases and aromatase expression increases as a result of the contribution to promoter I.f by transcriptional activators such as smads. However, since these putative cis-elements and transcription initiation sites are not conserved in the brain-specific promoter of other species, this transcriptional regulatory mechanism of exon I.f may be characteristic of Xenopus.

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Species referenced: Xenopus laevis
Genes referenced: cebpa crebbp cyp19a1 cyp26a1 ep300 foxd3 myc smad10 smad2 smad4 sox5