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DNA methylation is an important mechanism involved in embryogenesis and tumor development. Changing cytosines to 5-methylcytosines in CpG dinucleotides has been found to be responsible for the inactivation of tumor suppressor genes by repressing transcription. A central cell cycle regulator whose synthesis is controlled by transcription is cyclin B. In mammalian cells, cyclin B1 and B2 proteins are well characterized and often found to be overexpressed in cancer patients. Transcription from cyclin B1 and B2 promoters during the cell cycle is dependent upon a combination of two sites named ‘cell cycle-dependent element’ (CDE) and ‘cell cycle genes homology region’ (CHR), through repression in G0 and G1 followed by release in G2/M. Here we show that the cyclin B2 promoter contains a CpG island and that 5-aza-deoxycytidine treatment leads to deregulation of cell cycle-dependent mRNA expression from this gene via a loss of repression in G0. Furthermore, deletion of the DNA methyltransferase genes DNMT1 and DNMT3b leads to an increase in transcription of cyclin B2. Additionally, DNA methylation in vitro prevents transcriptional activation of the cyclin B2 promoter in G2/M. Analysis in vivo of the cyclin B2 core promoter revealed that the CDE/CHR site is partially methylated. However, quantitative in vivo analysis of the CpG-methylation level of the CDE during cell division indicates that CpG methylation is independent of the cell cycle. We conclude that DNA methylation affects cell cycle-dependent transcription of cyclin B2 but that regulation through CDE/CHR is independent of cytosine methylation.