Cross-talk between site-specific transcription factors and DNA methylation states

DNA methylation, which occurs predominantly at CpG dinucleotides, is a potent epigenetic repressor of transcription. BecauseDNAmethylation is reversible, there ismuchinterest in understanding the mechanisms by which it can be regulated by DNA-binding transcription factors. We discuss several models that, by incorporating sequence motifs, CpG density, and methylation levels, attempt to link the binding of a transcription factor with the acquisition or loss of DNA methylation at promoters and distal regulatory elements. Additional in vivo genome-wide characterization of transcription factor binding patterns and high-resolution DNA methylation analyses are clearly required for stronger support of each model.