Luciferase expression controlled by a viral gene promoter in a mammalian circadian pacemaker

Retinal light exposure induces several immediate-early genes in the hypothalamic suprachiasmatic nucleus (SCN), which contains the major circadian pacemaker of mammals. Clock-controlled and light-induced genes expressed in the SCN such as c-fos and mPer1 contain upstream regulatory elements similar to those of the major immediate-early gene (IE-1) of the human cytomegalovirus. IE-1 expression is critical for viral reactivation from latency and increases in response to agents acting through depolarization or the cAMP response element. To test whether IE-1 could be under circadian control, bioluminescence was imaged in individual SCN cells of brain slice cultures from transgenic mice containing the IE-1 enhancer/promoter upstream from the firefly luciferase gene luc. A small percentage of the cells in neonatal and adult cultures displayed circadian transgene expression, particularly ones near the dorsomedial edge of the SCN. Single-cell bioluminescence imaging revealed that the circadian pacemaker can regulate exogenous viral genes and could play a role in viral diseases.