Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene
Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene
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DOI：
10.1128/mcb.02227-07
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发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Ishida, Norio
中科院分区：
文献类型：
--
作者：
Onishi, Yoshiaki;Hanai, Syuji;Ishida, Norio
虽然Bmal 1是哺乳动物生物钟系统的一个关键组成部分，但人们对昼夜节律Bmal 1基因转录的实际机制知之甚少，特别是在染色质水平上。在这里，我们发现了一个独特的染色质结构内的Bmal 1启动子。RORE区域是Bmal 1基因昼夜节律调控的关键顺式元件，由富含GC的开放染色质组成。在体外报告基因测定中，即使在ROR α和REV-ERB α存在下，启动子的3 '侧翼区也抑制节律性转录。我们还发现，核基质蛋白SAF-A结合的3 '侧翼区与昼夜节律的时间，这是相关的Bmal 1表达的足迹在体内。这些结果表明，含有SAF-A的独特染色质结构是细胞中Bmal 1基因的昼夜转录调控所必需的。
Although Bmal1 is a key component of the mammalian clock system, little is understood about the actual mechanism of circadian Bmal1 gene transcription, particularly at the chromatin level. Here we discovered a unique chromatin structure within the Bmal1 promoter. The RORE region, which is a critical cis element for the circadian regulation of the Bmal1 gene, is comprised of GC-rich open chromatin. The 3'-flanking region of the promoter inhibited rhythmic transcription in the reporter gene assay in vitro even in the presence of ROR alpha and REV-ERB alpha. We also found that the nuclear matrix protein SAF-A binds to the 3'-flanking region with circadian timing, which was correlated with Bmal1 expression by footprinting in vivo. These results suggest that the unique chromatin structure containing SAF-A is required for the circadian transcriptional regulation of the Bmal1 gene in cells.