Mammalian methyl-binding proteins: what might they do?
CpG islands (CGIs) are regions enriched in the dinucleotide CpG; they constitute the promoter of about 60% of mammalian genes. In cancer cells, some promoter-associated CGIs become heavily methylated on cytosines, and the corresponding genes undergo stable transcriptional silencing. Hypermethylated CGIs attract methyl-CpG-binding proteins (MBPs), which have been shown to recruit chromatin modifiers and cause transcriptional repression. These observations have led to the prevalent model that methyl-CpG-binding proteins are promoter-proximal transcriptional repressors. Recent discoveries challenge this idea and raise a number of questions. Here we discuss the following issues: what are other possible roles for the known MBPs? Why are these proteins not essential in mammals? Are there other MBPs left to discover? Could CpG methylation be nonessential?
Joulie
Michael
M
CNRS UMR7216, Université Paris Diderot, Paris, France.
Miotto
Benoit
B
Defossez
Pierre-Antoine
PA
D000818:Animals; D042002:Chromatin Assembly and Disassembly; D018899:CpG Islands; D003596:Cytosine; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D037941:Silencer Elements, Transcriptional; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins; D003596:Cytosine