Direct regulation of CLOCK expression by REV-ERB.
Direct regulation of CLOCK expression by REV-ERB.
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DOI：
10.1371/journal.pone.0017290
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发表时间：
2011-03-29
期刊：
影响因子：
3.7
通讯作者：
Burris TP
中科院分区：
文献类型：
--
作者：
Crumbley C;Burris TP
昼夜节律在细胞水平上由转录反馈环调节，导致包括CLOCK、BMAL 1、PERIOD（PER）和CRY（CRY）在内的关键蛋白质表达的振荡。CLOCK和BMAL 1蛋白是bHLH类转录因子的成员，并形成调节PER和CRY基因表达的异源二聚体。核受体REV-ERBα通过直接结合BMAL 1启动子并在一天中REV-ERBα表达水平升高的特定时间抑制其表达，在BMAL 1表达的振荡调节中发挥关键作用。我们最近证实REV-ERBα还调节BMAL 1的异源二聚体伴侣NPAS 2的表达。在这里，我们发现REV-ERBα还调节BMAL 1的另一个异二聚体伴侣CLOCK的表达。我们使用染色质免疫沉淀-微阵列筛选在CLOCK基因的第一内含子内鉴定了REV-ERBα结合位点。抑制REV-ERBα表达导致CLOCK mRNA表达升高，这与REV-ERBα作为转录抑制因子的作用一致。REV-ERB反应元件（RevRE）在CLOCK基因的该区域内被鉴定，并且在人类和小鼠之间是保守的。此外，CLOCK RevRE赋予REV-ERB对异源报告基因的应答性。我们的数据表明，REV-ERBα通过调节BMAL 1和CLOCK基因的表达，在调节BMAL 1/CLOCK异源二聚体的活性中发挥双重作用。
Circadian rhythms are regulated at the cellular level by transcriptional feedback loops leading to oscillations in expression of key proteins including CLOCK, BMAL1, PERIOD (PER), and CRYPTOCHROME (CRY). The CLOCK and BMAL1 proteins are members of the bHLH class of transcription factors and form a heterodimer that regulates the expression of the PER and CRY genes. The nuclear receptor REV-ERBα plays a key role in regulation of oscillations in BMAL1 expression by directly binding to the BMAL1 promoter and suppressing its expression at certain times of day when REV-ERBα expression levels are elevated. We recently demonstrated that REV-ERBα also regulates the expression of NPAS2, a heterodimer partner of BMAL1. Here, we show that REV-ERBα also regulates the expression another heterodimer partner of BMAL1, CLOCK. We identified a REV-ERBα binding site within the 1st intron of the CLOCK gene using a chromatin immunoprecipitation – microarray screen. Suppression of REV-ERBα expression resulted in elevated CLOCK mRNA expression consistent with REV-ERBα's role as a transcriptional repressor. A REV-ERB response element (RevRE) was identified within this region of the CLOCK gene and was conserved between humans and mice. Additionally, the CLOCK RevRE conferred REV-ERB responsiveness to a heterologous reporter gene. Our data suggests that REV-ERBα plays a dual role in regulation of the activity of the BMAL1/CLOCK heterodimer by regulation of expression of both the BMAL1 and CLOCK genes.
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影响因子：
4
作者：
Meng QJ;McMaster A;Beesley S;Lu WQ;Gibbs J;Parks D;Collins J;Farrow S;Donn R;Ray D;Loudon A
通讯作者：
Loudon A
DOI：
10.1621/nrs.07003
发表时间：
2009
期刊：
Nuclear receptor signaling
影响因子：
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作者：
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通讯作者：
Jetten AM
影响因子：
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作者：
Stayrook, Keith R.;Rogers, Pamela M.;Burris, Thomas P.
通讯作者：
Burris, Thomas P.
影响因子：
4.8
作者：
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通讯作者：
Burris, Thomas P.
影响因子：
3.6
作者：
Wang, Yongjun;Rogers, Pamela M.;Burris, Thomas P.
通讯作者：
Burris, Thomas P.