Regulation Of Temporal And Spatial Gene Expression In Th

我们的单位感兴趣的是在昼夜节律时间框架基因表达调控模式的分子机制。在当前财年，我们一直专注于研究昼夜节律电子盒的上下文属性。这项工作很重要，因为E-box是一个极其混杂的DNA共识元素；因此，为了了解不同的信号通路如何区分不同的e -box，需要对原型启动子进行系统分析。在这种情况下，对抗利尿激素（AVP）启动子的分析导致了一种假定的新型转录因子的发现，该转录因子似乎是昼夜节律异二聚体BMAL/CLOCK的共同激活因子。在第二个项目中，我们正在研究BMAL/CLOCK结合在特定启动子上的可能性，它可能作为一种延迟装置，延迟cAMP介导的对其他在关键位置包含完美e - box的昼夜节律基因的刺激。第三个项目涉及特定AP-1复合物对时钟控制基因的作用机制，它似乎能够通过间接途径对BMAL/时钟介导的激活施加强大的抑制。

Our Unit is interested in the molecular mechanisms underlying regulated patterns of gene expression in circadian time frames. During the current FY we have been focusing our studies on the contextual properties of circadian E-boxes. This work is important because the E-box is an extremely promiscuous DNA consensus element; thus, in order to understand how different signaling pathways can differentiate among different E-boxes, a systematic analysis of prototypic promoters is needed. The analysis of the vasopressin (AVP) promoter in this context led to the discovery of a putative novel transcription factor which appears to function as a co-activator of the circadian heterodimer BMAL/CLOCK. In a second project we are investigating the possibility that BMAL/CLOCK binding on specific promoters may act as a delaying device to postpone the cAMP mediated stimulation of other circadian genes that contain perfect E-Boxes at critical locations. A third project involves the mechanism of action of specific AP-1 complexes on clock controlled genes, which appear to be able to exert powerful suppression of BMAL/Clock mediated activation via an indirect pathway. Lastly, we have recently made the exciting observation of a thermogenesis-related gene displaying sex specific, tissue restricted and circadian expression in the rodent system. Its promoter is being analyzed to understand the mechanisms underlying such a complex pattern of expression.