کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1953107 1057251 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
cyclicAMP and glucocorticoid responsiveness of the rat carbamoylphosphate synthetase gene requires the interplay of upstream regulatory units
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
cyclicAMP and glucocorticoid responsiveness of the rat carbamoylphosphate synthetase gene requires the interplay of upstream regulatory units
چکیده انگلیسی
Many genes involved in metabolic processes are regulated by glucocorticoids and/or cyclicAMP. The hepatic expression of the urea cycle enzyme carbamoylphosphate-synthetase-I gene (CPS) is regulated at the transcriptional level by both factors. Here, we report that the 5′ half of the distal enhancer is necessary and sufficient for full cyclicAMP responsiveness. The cyclicAMP-responsive element (CRE), and FoxA- and C/EBP-binding sites are indispensible for cyclicAMP responsiveness, indicating that these elements make up a cyclicAMP-responsive unit (CRU). In addition to this CRU, the CPS regulatory regions contain two glucocorticoid-response elements (GRE): one in the 3′ region of the distal enhancer and one in the proximal enhancer. In presence of the cyclicAMP-responsive region in the distal enhancer, only one of the GREs is required for glucocorticoid-inducible CPS expression, with both GREs acting in an additive fashion to fully confer the inducing effect of glucocorticoids. In contrast, the simultaneous presence of both GREs is required in the absence of the cyclicAMP-responsive region. In this configuration, the distal GRE fully depends on its neighbouring FoxA and C/EBP REs for activity and is, therefore, a glucocorticoid-responsive unit. In conclusion, we show here that the CPS CRU is a bifunctional unit that elicits the cyclicAMP response and, in addition, functions as a glucocorticoid accessory unit to establish a glucocorticoid response from otherwise silent proximal or distal GRUs. Therefore, cyclicAMP and glucocorticoid pathways can induce CPS transcription via overlapping sets of response elements.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 89, Issue 5, May 2007, Pages 574-580
نویسندگان
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