Epidermal growth factor receptor-induced circadian-time-dependent gene regulation in suprachiasmatic nucleus

A significant functional role for epidermal growth factor receptor (EGFR) in the suprachiasmatic nucleus is suggested by recent findings that epidermal growth factor receptor and its ligand transforming growth factor-&agr; are highly expressed in the suprachiasmatic nucleus. Recent studies indicate that epidermal growth factor receptor activation induces behavioral and physiological effects, strengthening the notion that epidermal growth factor receptor can modulate suprachiasmatic nucleus neural function and behavior. A global transcriptional profiling study is performed to investigate the gene expression response to epidermal growth factor receptor activation in the suprachiasmatic nucleus. The results indicate that all of the observed gene expression response is circadian-time dependent. The response included several genes encoding different neuropeptide receptors, ion channels and kinases. In order to hypothesize the transcription factors underlying the epidermal growth factor receptor response, different circadian-time-dependent gene expression groups were analyzed for enriched transcriptional regulatory elements in the promoters. The results indicate that several transcription factors such as Elk1 and cAMP-responsive element binding protein/activating transcription factor family, known to be ‘input points’ to the core clock network, are playing a role. Together, these results indicate that epidermal growth factor receptor has a circadian-time-dependent neuromodulatory function in the suprachiasmatic nucleus.