Estrogen-related receptor α, the molecular clock, and transcriptional control of metabolic outputs

Metabolism and circadian rhythms must be closely integrated to support the energetic needs of the organism linked to the daily timing of physiological and behavioral processes. Although components of the molecular clock can directly target some metabolic genes, the control of metabolic clock output is believed to be mediated mostly through the action of transcription factors whose patterns of expression are rhythmic in metabolic tissues. Our recent work has identified the orphan nuclear receptor estrogen-related receptor α (ERRα), a potent effector of metabolic gene networks, as a direct regulator of the molecular clock. Thus, by acting both upstream of and downstream from the molecular clock, ERRα serves as a key transcription factor linking the clock with metabolic control.