Yanagisawa Yuka, Ito Emi, Yuasa Yasuhito, Maruyama Kazuo
Department of Molecular Oncology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan.
Biochim Biophys Acta. 2002 Sep 27;1577(3):457-65. doi: 10.1016/s0167-4781(02)00482-7.
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.
由从头甲基化建立的DNA修饰参与基因组功能的表观遗传控制。DNMT3A和DNMT3B基因编码假定的从头甲基转移酶。在本文中，我们研究了人类DNMT3A和DNMT3B基因的转录调控区域。我们发现DNMT3A和DNMT3B基因有多个转录起始点（TSP），这些转录起始点在染色体上是分开的，并且这些基因的表达由多个启动子控制。DNMT3A基因至少有四个TSP，其表达由三个不同的启动子控制。所有这三个启动子在TSP附近都缺乏典型的TATA序列。其中两个带有富含CpG的启动子，另一个是CpG含量低的启动子。DNMT3B基因至少有两个TSP，它们存在于不同的外显子中，其表达由不同的启动子控制。DNMT3B基因的两个启动子区域都缺乏典型的TATA序列，其中一个启动子在TSP附近含有一个富含CpG的区域，另一个启动子的CpG含量低。结合人类DNMT1基因既有富含CpG的启动子又有CpG含量低的启动子这一数据，表明富含CpG和CpG含量低这两种类型的启动子进行转录调控可能是DNMT基因家族的共同特征。
