Circadian System: Temporal and Spatial Gene Expression

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。昼夜节律领域为假设驱动的研究最适合填补的空白类型提供了很好的例子。时间基因表达单元的长期目标是确定在昼夜节律系统中控制基因表达特异性的机制。我们的具体目标是确定DNA位点和蛋白质因子的功能，以实现a)昼夜节律目标选择（激活哪个基因和在哪里激活？）和b)精确的幅度调节（多少？）。

Our Unit is interested in the molecular mechanisms underlying regulated patterns of gene expression in circadian time frames. The circadian field provides excellent examples of the types of gaps that hypothesis-driven research is best suited to fill. The long-term goal of the Unit on Temporal Gene Expression is to identify the mechanisms controlling the specificity of gene expression in the circadian system. Our specific aim is to identify DNA sites and protein factors that function to achieve a) circadian target selection (which gene to activate and where?) and b) precise amplitude modulation (by how much?). We have identified a novel accessory sequence upstream of the vasopressin E-box which plays a role in maximizing the response of the adjacent E-box towards the circadian BMAL/CLOCK heterodimer. We have further discovered that photic input can modulate DNA binding activity towards this element in the suprachiasmatic nucleus and in the pineal gland. Follow up studies have prompted us to take a closer look at zinc homeostasis by light in photically driven organs. In addition, we have established that the transcripton factor sterol response element binding factor (SREBP)-1 plays a likely role in the integration of circadian and nutritional cues in the liver, a finding that opens up new avenues of research towards a better understanding of transcription organization by converging, and sometimes conflicting, pathways.