DNA methylation levels differed markedly among the three CpG promoter density profiles at the early neurulation stage. The incidence of hypermethylation in HCP was low, correlating with active transcription at the beginning of neurulation, a period of rapid growth. In addition, the number of expressed genes was two-fold greater than in the HCP than in the LCP promoter group, in agreement with a previous study,56 predicting expression of more housekeeping and developmental genes than tissue-specific genes at this early stage of development. This DNA methylation-to-transcription trend was much less apparent in the lower promoter CpG density genes; i.e., in the ICP group, about 1/3 of genes were hypermethylated (Fig. 2C) while 1/2 of genes were silent (Fig. 3A). In the LCP group, most of the genes remained silent but not hypermethylated. Although our findings demonstrate a strong reverse correlation of gene expression level with methylation level, we are not attempting to absolutely link hypomethylation and gene expression. For instance in HCP, 3% genes are hypermethylated, while 76.6% are expressed. However, for individual genes, the expression level is dependent on the
