Transcriptional Regulation of the AhR Gene during Adipose Differentiation(Biochemistry/Molecular Biology)

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The aryl hydrocarbon receptor (AhR) mediates a spectrum of toxicological and biological effects of dioxins. Studies on tissue distribution of the AhR in developing and adult animals demonstrated that the AhR is expressed in a tissue-specific and developmentally specific manner. Also, the expression level of the AhR in culture cells varies more than 50-fold among cell lines. Although the mode of AhR action has been studied extensively, the events that control the expression of the AhR gene itself are still poorly understood. We previously showed that the AhR protein is depleted during adipose differentiation, resulting in the loss of functional response to xenobiotics. In this study, to understand the mechanism by which the AhR is depleted during adipogenesis, we analyzed the AhR promoter activity during adipose differentiation in 3T3-L1 cells. Nuclear run-on assay revealed that the downregulation of the AhR during adipogenesis is primarily at the transcriptional level. To identify the sequence of the AhR promoter region responsible for differentiation-dependent suppression of AhR transcription, a series of deletion constructs linked to the CAT reporter were transfected into 3T3-L1 cells. A comparison of CAT activity between preadipocytes and adipocytes revealed that the sequence -378/-359 is core contributor to differentiation-dependent downregulation of AhR promoter activity. EMSA and UV crosslinking studies showed the presence of the factor bound to the sequence -378/-359. The binding activity was apparently higher in preadipocytes than in adipocytes. Consequently, the downregulation of the trans-acting factor may result in the suppression of AhR gene transcription during adipose differentiation.
公益社団法人日本薬学会の論文
2003-09-01

Transcriptional Regulation of the AhR Gene during Adipose Differentiation(Biochemistry/Molecular Biology)

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