Sp1 binding is inhibited by mCpmCpG methylation
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 mCpmCpG inhibits binding by 95 …
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 mCpmCpG inhibits binding by 95 …
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 mCpmCpG inhibits binding by 95%. Furthermore, we have identified endogenous mCpmCpG 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 mCpmCpG 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.
Elsevier