Transcriptional regulation of the gene encoding the StAR protein in the human adrenocortical cell line, H295R by cAMP and TGFbeta1.
In the present work, we have analyzed the transcriptional regulation of StAR expression in the human adrenocortical cell line H295R. We observed that StAR mRNA levels rapidly increased in response to forskolin, starting after 2 h of treatment and reaching a maximum by 12 h. Deletion analysis of the human StAR promoter demonstrated that the first 150 bp upstream of the transcription start were sufficient for both basal and cAMP-induced expression of a reporter gene. We demonstrate that out of the three binding sequences for the steroidogenic factor 1 (SF-1) only the central one (-105 to -96) is implicated in both basal and cAMP-induced StAR expression. In addition, another important regulatory element for both basal and cAMP-induced StAR expression is present between -62 and -24 upstream of the transcription start. We also show that TGF1beta1 inhibits StAR expression at the transcriptional level. We found that the TGFbeta-inhibitory element lies between -150 and -85 upstream of the transcription start and that the SF-1 binding sites are not implicated in TGFbeta1 regulation.
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INSERM Unité 244, Département de Biologie Moléculaire et Structurale, CEA-Grenoble, France.
Nury
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Chambaz
E M
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Feige
J J
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Bailly
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D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D017930:Genes, Reporter / Q000502:physiology; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000098682:Steroidogenic Acute Regulatory Protein; D005576:Colforsin; D000242:Cyclic AMP