Transcriptional regulation of the human aromatase cytochrome P450 gene expression in human placental cells.
The human aromatase cytochrome P450 gene, CYP 19, spans more than 75 kb in the human genome. Recently, it is proposed that the expression of the CYP 19 gene is regulated in part by tissue-specific promoters through the use of mechanisms involving alternative splicing of a number of untranslated exons. In this study, we have characterized cis-acting elements involved in the transcriptional regulation of the gene in human placental cells, where the majority of the transcripts contain the 5'-untranslated sequence encoded by exon I.1. By transient expression analyses in human BeWo choriocarcinoma cells using the bacterial chloramphenicol acetyltransferase gene as a reporter gene, we localized an enhancer element in the region between -242 and -166 relative to the major cap site of the gene. Furthermore, we demonstrate that the element between -2141 and -2115 participates in the 12-O-tetradecanoylphorbol 13-acetate (TPA)-mediated enhancement of gene expression. By screening a human placental cDNA expression library, we have isolated a cDNA clone (lambda 1-2) encoding a peptide which binds specifically to the element between -2141 and -2115. Sequence analysis of the clone revealed that the insert of lambda 1-2 encodes a part of the amino acid sequence of NF-IL6 (also termed as LAP and C/EBP beta). Northern blot analysis reveals expression of the NF-IL6 gene in BeWo cells and human placenta. These results indicate that NF-IL6 is one of the nuclear factors which participate in TPA-mediated transcriptional enhancement of CYP 19 gene expression.
Toda
K
K
Department of Medical Chemistry, Kochi Medical School, Japan.
Yang
L X
LX
Shizuta
Y
Y
D000595:Amino Acid Sequence; D001141:Aromatase / Q000235:genetics*; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010920:Placenta / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D001141:Aromatase; D013755:Tetradecanoylphorbol Acetate