Various physiological processes and behaviors show a circadian rhythm of approximately 24 h, which is crucial in coordinating internal metabolic processes and environmental signals. Post-translational modifications play an important role in regulating circadian core proteins. In this study, we demonstrated that BMAL1 was modified with an O-linked beta-N-acetylglucosamine (O-GlcNAc), which stabilized BMAL1 and enhanced its transcriptional activity. Conversely, inhibition of O-GlcNAcylation resulted in inhibition of circadian rhythms of clock gene expression. Because O-GlcNAcylation is sensitive to the glucose level, such a modification may provide a new mechanism connecting metabolism with circadian rhythms. (C) 2013 Elsevier Inc. All rights reserved.