In cancer cells, methylation-dependent gene silencing is at least partly mediated by the “Methyl-CpG-Binding Domain protein
2” (MBD2 protein), via the recruitment of chromatin remodeling complexes. However this repressive role was poorly investigated in
normal cells. To identify the genes repressed by MBD2 in these cells, we have determined the impact of MBD2 depletion on gene expression
in human embryonic MRC5 fibroblasts, using RNA inference combined with microarray analysis. The up-regulation of some
randomly selected genes was confirmed and a direct association between gene repression and MBD2 binding on methylated promoters
associated to these genes was subsequently established. This control of gene expression appears to depend on the CpG content of promoters
as MBD2 depletion was not sufficient to induce the expression of silent genes associated with High-CpG promoters, but it was required
to achieve the methyl-dependent transcriptional locking of the genes associated with promoters exhibiting intermediate CpG content.
Therefore, MBD2 seems to play a selective role in gene repression depending on the CpG content of the promoter regions.
Keywords: DNA methylation, methyl-DNA binding protein, transcription, CpG.
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