Flexible phase adjustment of circadian albumin D site-binding protein (Dbp) gene expression by CRYPTOCHROME1
Flexible phase adjustment of circadian albumin D site-binding protein (Dbp) gene expression by CRYPTOCHROME1
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DOI：
10.1101/gad.578810
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发表时间：
2010-06-15
影响因子：
10.5
通讯作者：
Ripperger, Juergen A.
中科院分区：
文献类型：
--
作者：
Stratmann, Markus;Stadler, Frederic;Ripperger, Juergen A.
白蛋白D位点结合蛋白（DBP）在小鼠的活动期和随后的食物摄入之前控制许多肝脏解毒和代谢酶的昼夜节律转录。然而，小鼠的行为受到光周期的严重影响。因此，在肝脏中需要持续调节昼夜Dbp表达的相位。在这里，我们描述了一个直接的影响，β-PTOCHROME 1（β-1）的相位Dbp的表达。DBP和核受体Rev-Erb α是BMAL 1和CLOCK的昼夜节律靶基因。令人惊讶的是，与Rev-Erb α相比，动态结合到Dbp启动子区域的BMAL 1和CLOCK介导的Dbp转录延迟。在细胞核中延长存在的BMP 1使得在从短到长的光周期变化时，Dbp的相位与Rev-Erb α表达连续解偶联。因此，APP 1保持DBP积累的峰值接近活动期。相比之下，Rev-Erb α表达被相位锁定到昼夜节律振荡器，并通过其自身基因产物的积累而形成。我们的数据表明，肝脏中昼夜节律转录的微调比预期的更复杂。
The albumin D site-binding protein (DBP) governs circadian transcription of a number of hepatic detoxification and metabolic enzymes prior to the activity phase and subsequent food intake of mice. However, the behavior of mice is drastically affected by the photoperiod. Therefore, continuous adjustment of the phase of circadian Dbp expression is required in the liver. Here we describe a direct impact of CRYPTOCHROME1 (CRY1) on the phase of Dbp expression. Dbp and the nuclear receptor Rev-Erb alpha are circadian target genes of BMAL1 and CLOCK. Surprisingly, dynamic CRY1 binding to the Dbp promoter region delayed BMAL1 and CLOCK-mediated transcription of Dbp compared with Rev-Erb alpha. Extended presence of CRY1 in the nucleus enabled continuous uncoupling of the phase of Dbp from Rev-Erb alpha expression upon change from short to longer photoperiods. CRY1 thus maintained the peak of DBP accumulation close to the activity phase. In contrast, Rev-Erb alpha expression was phase-locked to the circadian oscillator and shaped by accumulation of its own gene product. Our data indicate that fine-tuning of circadian transcription in the liver is even more sophisticated than expected.