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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cell-type-specific binding of the transcription factor CREB to the cAMP-response element
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Cell-type-specific binding of the transcription factor CREB to the cAMP-response element

机译:转录因子CREB与cAMP反应元件的细胞类型特异性结合

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The cAMP-response element-binding protein (CREB) transcription factor was initially identified as a mediator of cAMP-induced gene expression. CREB binds to a target sequence termed the cAMP-response element (CRE) found in many cellular and viral gene promoters. One of the best-characterized CRIES resides in the promoter of the gene encoding the neuropeptide somatostatin, and this element has served as a model for studies of CREB function. Phosphorylation of CREB by protein kinase A allows recruitment of the coactivator CREB-binding protein (CBP). A central tenet of the CREB-CBP model is that CREB binds constitutively to the CRE and that regulation occurs through the phosphorylation-dependent recruitment of CBP. In this report, we use chromatin immunoprecipitation assays to show that CREB does not interact in vivo with the somatostatin CRE, or similar elements in several other genes, in PC12 cells, a standard model for studies of CREB function. Rather, CREB binding in vivo is regulated in a cell-specific manner, a finding that was confirmed by using in vivo genomic footprinting assays. The CREs in other genes were also found to interact differentially with CREB in PC12 cells, hepatoma cells, and cortical neurons. We conclude that the family of CREB target genes differs from one cell type to another and that the ability of CREB to bind to a particular CRE represents an important component of gene regulation.
机译:最初将cAMP反应元件结合蛋白(CREB)转录因子鉴定为cAMP诱导的基因表达的介质。 CREB与在许多细胞和病毒基因启动子中发现的称为cAMP反应元件(CRE)的靶序列结合。最典型的CRIES之一位于编码神经肽生长抑素的基因的启动子中,该元件已成为研究CREB功能的模型。蛋白激酶A使CREB磷酸化,可以募集共激活剂CREB结合蛋白(CBP)。 CREB-CBP模型的中心原则是CREB与CRE组成性结合,并且通过磷酸化依赖性CBP募集进行调节。在本报告中,我们使用染色质免疫沉淀测定法来显示CREB在PC12细胞(CREB功能研究的标准模型)中与生长抑素CRE或其他几个基因中的相似元素在体内不发生相互作用。而是,CREB在体内的结合是以细胞特异性方式调节的,这一发现已通过体内基因组足迹测定法得到证实。还发现其他基因中的CRE与PC12细胞,肝癌细胞和皮层神经元中的CREB相互作用不同。我们得出的结论是,CREB靶基因家族从一种细胞类型到另一种细胞类型是不同的,并且CREB结合特定CRE的能力代表了基因调控的重要组成部分。

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