Dear Editor,DNA methylation at the 5-position of cytosine (5mC) is a crucial epigenetic mark in regulating biological processes including gene silencing,gene imprinting,and X chromosome inactivation (Jaenisch and Bird,2003;Smith and Meissner,2013).Human genome encodes three DNA methyltransferases,DNMT1,DNMT3A and DNMT3B to catalyze 5mC.Although not tightly restricted,DNMT1 is thought to maintain the established patte of 5mC throughout DNA replication,while DNMT3A and DNMT3B are largely responsible for the de novo establishment of 5mC.It has long been questioned how de novo DNA 5mC pattes are established in different genomic regions and whether histone modifications crosstalk to the process.Until recently,it was reported that through recognition of histone H3K36me3 mark,DNMT3B plays a dominant role in mediating DNA 5mC in the genic region undergoing active transcription (Baubec et al.,2015;Neri et al.,2017).However,5mC occurs at both intergenic and genic regions,while H3K36me3 is largely absent in the intergenic regions,indicating that the intergenic 5mC may be mediated through different mechanisms.