The human DNA methyltransferases DNMT3A and DNMT3B have two types of promoters with different CpG contents.

DNA modification that is established by de novo methylation is involved in the epigenetic control of genome functions. The DNMT3A and DNMT3B genes encode putative de novo methyltransferases. In this paper, we investigated the transcriptional regulatory regions of the human DNMT3A and DNMT3B genes. We found that the DNMT3A and DNMT3B genes have multiple transcriptional start points (TSPs) that are separated on the chromosome and the expressions of these genes are controlled by multiple promoters. The DNMT3A gene has at least four TSPs and the expression is controlled by three different promoters. All three promoters lack typical TATA sequences adjacent to the TSPs. Two of them bear CpG-rich promoters and the other a CpG-poor promoter. The DNMT3B gene has at least two TSPs which exist in different exons and the expression is controlled by different promoters. Both promoter regions of the DNMT3B gene lack typical TATA sequences, where one promoter contains a CpG-rich area near the TSP, the other promoter is CpG-poor. Together with the data that the human DNMT1 gene has both CpG-rich and CpG-poor promoters, it is suggested that transcriptional regulation by two types of promoters, CpG-rich and CpG-poor, might be common characteristics in the DNMT gene family.