The circadian rhythm is originally generated by a transcription-translation based oscillatory loop composed of a set of clock genes in most organisms. The clock gene oscillation is generated by the core loop in each neuron of the hypothalamic suprachiasmatic nucleus. Phosphorylation and ubiquitination of clock proteins play the crucial role for the rhythmic transcription of clock genes. The core clock oscillation is conducted at the cellular levels by E-box or by D-box of clock controlled genes.