Circadian System: Temporal and Spatial Gene Expression

我们的单位感兴趣的是在昼夜节律的时间框架基因表达的调控模式的分子机制。昼夜节律场提供了假设驱动研究最适合填补的空白类型的绝佳例子。时间基因表达单元的长期目标是确定控制昼夜节律系统中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，其功能是实现a）昼夜节律靶向选择（激活哪个基因，在哪里？）和B）精确的幅度调制（多少？）。 我们已经确定了一种新的辅助序列上游的加压素E盒，发挥了最大限度地提高响应相邻的E盒对昼夜BMAL/时钟异二聚体的作用。我们进一步发现，光输入可以调节DNA结合活性，对这个元素在视交叉上核和松果体。后续研究促使我们更仔细地观察光驱动器官中的锌稳态。 此外，我们已经确定转录因子固醇反应元件结合因子（SREBP）-1在肝脏昼夜节律和营养线索的整合中起着可能的作用，这一发现开辟了新的研究途径，通过融合，有时是冲突的途径更好地了解转录组织。

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.