DNA methylation is a key epigenetic mark when occurring in the promoter and enhancer regions regulates the accessibility of the binding protein and gene transcription. DNA methylation is inheritable and can be de novo-synthesized, erased and reinstated, making it arguably one of the most dynamic upstream regulators for gene expression and the most influential pacer for development. Recent progress has demonstrated that two forms of cytosine methylation and two pathways for demethylation constitute ample complexity for an instructional program for orchestrated gene expression and development. The forum of the current discussion and review are whether there is such a program, if so what the DNA methylation program entails, and what environment can change the DNA methylation program. The translational implication of the DNA methylation program is also proposed.
Keywords: 5-hydroxymethylcytosine; DNA demethylation; environmental factors; epigenetics; epigenome; neural development.