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 i s 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.
