Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1.
Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1.
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DOI：
10.3389/fnmol.2017.00413
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发表时间：
2017
影响因子：
4.8
通讯作者：
Murphy D
中科院分区：
文献类型：
--
作者：
Greenwood MP;Greenwood M;Gillard BT;Chitra Devi R;Murphy D
环腺苷酸（cAMP）诱导型转录因子cAMP反应元件结合蛋白3样1（Creb 3l 1）在下丘脑中强烈激活，以响应高渗提示，如脱水（DH）。我们最近发现，Creb 3l 1表达上调cAMP途径在体外，但确切的机制是未知的。在这里，我们表明，通过提高小鼠垂体AtT 20细胞中的cAMP水平来增加Creb 3l 1的转录，自动启动Creb 3l 1的裂解，从而导致更丰富的转录活性N-末端部分。抑制蛋白质合成表明，从头蛋白质合成的中间转录因子Creb 3l 1诱导所需的。我们的微阵列数据从脱水啮齿动物下丘脑的战略挖掘揭示了四个候选人，减少到两个通过分析急性高血压诱导的下丘脑的转录激活配置文件，和一个，孤儿核受体Nr 4a 1，通过直接shRNA介导的沉默AtT 20细胞。我们发现，激活Creb 3l 1转录Nr 4a 1涉及与一个单一的NBRE网站在启动子区的相互作用。通过该途径在体外激活Creb 3l 1转录的能力取决于该基因近端启动子/5′UTR内CpG岛的甲基化水平。因此，我们确定了一种新的cAMP-Nr 4a 1-Creb 3l 1转录途径在AtT 20细胞，也，我们的证据表明，在下丘脑。
Cyclic AMP (cAMP) inducible transcription factor cAMP responsive element binding protein 3 like 1 (Creb3l1) is strongly activated in the hypothalamus in response to hyperosmotic cues such as dehydration (DH). We have recently shown that Creb3l1 expression is upregulated by cAMP pathways in vitro, however the exact mechanisms are not known. Here we show that increasing Creb3l1 transcription by raising cAMP levels in mouse pituitary AtT20 cells automatically initiates cleavage of Creb3l1, leading to a greater abundance of the transcriptionally active N-terminal portion. Inhibiting protein synthesis indicated that de novo protein synthesis of an intermediary transcription factor was required for Creb3l1 induction. Strategic mining of our microarray data from dehydrated rodent hypothalamus revealed four candidates, reduced to two by analysis of acute hyperosmotic-induced transcriptional activation profiles in the hypothalamus, and one, orphan nuclear receptor Nr4a1, by direct shRNA mediated silencing in AtT20 cells. We show that activation of Creb3l1 transcription by Nr4a1 involves interaction with a single NBRE site in the promoter region. The ability to activate Creb3l1 transcription by this pathway in vitro is dictated by the level of methylation of a CpG island within the proximal promoter/5′UTR of this gene. We thus identify a novel cAMP-Nr4a1-Creb3l1 transcriptional pathway in AtT20 cells and also, our evidence would suggest, in the hypothalamus.
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影响因子：
4.8
作者：
Greenwood MP;Greenwood M;Paton JF;Murphy D
通讯作者：
Murphy D
影响因子：
7.7
作者：
Denard B;Lee C;Ye J
通讯作者：
Ye J
影响因子：
2.5
作者：
Ahn JI;Yoo JY;Kim TH;Kim YI;Ferguson SD;Fazleabas AT;Young SL;Lessey BA;Ahn JY;Lim JM;Jeong JW
通讯作者：
Jeong JW
影响因子：
3.2
作者：
Greenwood MP;Greenwood M;Gillard BT;Loh SY;Paton JF;Murphy D
通讯作者：
Murphy D
影响因子：
3.7
作者：
Greenwood M;Greenwood MP;Paton JF;Murphy D
通讯作者：
Murphy D