Characterization of a cis-acting element involved in cell-specific expression of the zebrafish brain aromatase gene.
The cytochrome P450 Aromatase is the key enzyme catalyzing the conversion of androgens into estrogens. In zebrafish, the brain aromatase is encoded by cyp19b. Expression of cyp19b is restricted to radial glial cells bordering forebrain ventricles and is strongly stimulated by estrogens during development. At the promoter level, we have previously shown that an estrogen responsive element (ERE) is required for induction by estrogens. Here, we investigated the role of ERE flanking regions in the control of cell-specific expression. First, we show that a 20 bp length motif, named G x RE (glial x responsive element), acts in synergy with the ERE to mediate the estrogenic induction specifically in glial cells. Second, we demonstrate that, in vitro, this sequence binds factors exclusively present in glial or neuro-glial cells and is able to confer a glial specificity to an artificial estrogen-dependent gene. Taken together, these results contribute to the understanding of the molecular mechanisms allowing cyp19b regulation by estrogens and allowed to identify a promoter sequence involved in the strong estrogen inducibility of cyp19b which is specific for glial cells. The exceptional aromatase activity measured in the brain of teleost fish could rely on such mechanisms.
Le Page
Yann
Y
Université de Rennes 1, UMR CNRS 6026, Interactions Cellulaires et Moléculaires, Rennes, France.
Menuet
Arnaud
A
Kah
Olivier
O
Pakdel
Farzad
F
D000818:Animals; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D001921:Brain / Q000201:enzymology*; D002460:Cell Line; D004967:Estrogens / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009154:Mutation; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000096:biosynthesis* / Q000235:genetics
D004967:Estrogens; D029961:Zebrafish Proteins; D001141:Aromatase; C440728:Cyp19a1b protein, zebrafish