Molecular Mechanism Of Transcriptional Factors Mediated Passive DNA Demethylation

The balance between DNA methylation and DNA demethylation maintains the methylation spectrum of genomic DNA.The DNA demethylation involves active and passive approaches.Actually,passive DNA demethylation is mainly caused by impeding the sustainability of DNA methylation via a replication-dependent dilution effect.However,the detailed mechanisms of passive DNA demethylation remain to be studied.UHRF1 is an important regulator of DNA methylation.Previous studies showed that DNMT1 is recruited by UHRF1,which binds hemimethylated DNA by a unique SRA domain,to methylate newly replicated DNA.Transcription factors have the ability of binding DNA.Assuming that transcription factors can also bind to hemimethylated DNA,will they inhibit UHRF1 to bind the hemimethylated DNA?In order to address these questions,we tested the binding of several transcription factors to hemimethylated DNA and their binding to hemimethylation DNA with the presence of UHRF1.We found that transcription factors C-MYC,NANOG,KLF4 and SP1 can bind to hemimethylated DNA.By competitive DNA binding assay,we found that C-MYC,NANOG,KLF4,SP1 and E2F1 all inhibited the binding of UHRF1 to hemimethylated DNA.We also found that NANOG can interact with UHRF1.Thus,our study provides evidence that transcription factors can inhibit the binding of UHRF1 to hemimethylated DNA by competition,and thereby represents a vital mechanism for DNA passive demethylation.