Cytosine methylation transforms an E2F site in the retinoblastoma gene promoter into a binding site for the general repressor methylcytosine-binding protein 2 (MeCP2)
B. Di Fiore et al., Cytosine methylation transforms an E2F site in the retinoblastoma gene promoter into a binding site for the general repressor methylcytosine-binding protein 2 (MeCP2), NUCL ACID R, 27(14), 1999, pp. 2852-2859
The CpG-rich promoter of the retinoblastoma tumor suppressor gene (Rb-1) is
normally unmethylated, However, aberrant methylation of CpG dinucleotides
within the Rb-1 promoter has been depicted in certain tumors, which determi
nes transcriptional inactivity of the gene and absence of the pRb retinobla
stoma protein. Here we have concentrated on an E2F-binding site in the Rb-1
promoter. We show that the E2F site is required for cell-cycle regulated R
b-1 transcription in non-transformed cells. The function of the E2F site is
associated with its ability to interact with several activating factors of
the E2F family. In contrast, in vitro methylation of two tandemly arranged
CpGs in the E2F recognition site prevents binding by E2F factors, and dete
rmines instead the recruitment of the general repressor methylcytosine-bind
ing protein 2 (MeCP2), These results suggest that the interaction of MeCP2
with the methylated version of the E2F site may represent a step towards Rb
-1 promoter inactivity in tumor cells.