Methylation surrounding CpG islands is not always associated with high gene expression Dajun Deng, Peking University Cancer Hospital and Institute 12 February 2015 It is well recognized that methylation of CpG islands is initiated from methylation seeding sites flanking CpG islands, which are called as CpG island shores or sequences surrounding CpG islands. Indeed, when methylation of CpG sites occurs only in the shore region, gene transcriptional activity is not silenced, as reported by Edgar et al. in this meta-analysis paper. However, when methylation of CpG sites is extended to CpG islands, especially to whole CpG island, these genes are epigenetically inactivated. In many cases, both CpG islands and shore regions are not methylated in the 5' regions surrounding transcription starting sites within actively expressed genes. In contrast, occurrence of methylation in these shores imply the tendency of establishment of methylation of CpG islands. Therefore, it should be aware that the reported association between shore methylation and high gene expression in this paper maybe not ture when the flanking CpG islands are methylated. Competing interests I have no potential conflicts of interests.