Background:The regulation of the core clock gene Bmal1 is not fully understood despite many studies. Results: NF-Y cooperates with Sp1 to activate the transcription of Bmal1 by binding to the CCAAT-boxes in the Bmal1 promoter. Conclusion: NF-Y/Sp1 and Rev-Erb␣ serve as positive and negative regulators of Bmal1 expression, respectively. Significance: Elucidation of Bmal1 regulation provides a better understanding of its biological functions and the circadian clock overall.