Sp1 binding is inhibited by (m)Cp(m)CpG methylation

Gene. 1997 Aug 11;195(1):67-71. doi: 10.1016/s0378-1119(97)00164-9.


Previously it has been found that binding of the Sp1 transcription factor is not significantly affected by methylation of the CpG dinucleotide within its binding site, 5'-GGGCGG (lower strand, 5'-CCGCCC). Since it has been established that mammalian cells also have the capacity to methylate cytosines (C) at CpNpG sites we examined the effect of methylation of the outer C of the CpCpG on Sp1 binding. We find that methylation of the outer C is inhibitory and in particular methylation of both cytosines (m)Cp(m)CpG inhibits binding by 95%. Furthermore, we have identified endogenous (m)Cp(m)CpG methylation of an Sp1 site in the CpG island promoter of the retinoblastoma (Rb) gene by genomic sequencing. This occurs in a proportion of retinoblastoma tumors which are extensively CpG methylated in the Rb promoter. The results raise the possibility that (m)Cp(m)CpG methylation could have a biological function in preventing Sp1 binding, thereby contributing to the subsequent abnormal methylation of CpG islands often observed in tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cytosine / metabolism
  • DNA Methylation*
  • Molecular Sequence Data
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*


  • Oligonucleotides
  • Retinoblastoma Protein
  • Sp1 Transcription Factor
  • Cytosine

Associated data

  • GENBANK/L11910