Abstract
Methylation of DNA in mammalian cells serves to demarcate functionally specialized regions of the genome and is strongly associated with transcriptional repression. A highly conserved family of DNA-binding proteins characterized by a common sequence motif is widely believed to convert the information represented by methylation patterns into the appropriate functional state. This family, the MBD family, has been characterized at both the biochemical and genetic levels. A key issue, given their highly similar DNA-binding surfaces, is whether the individual MBD proteins bind differentially to distinct regions within the genome and, if so, by what mechanism. Somewhat surprisingly, some MBD family members, such as MeCP2, have considerable selectivity for specific sequences. Other family members, such as MBD2, appear to bind with somewhat relaxed specificity to methylated DNA. Recent genetic and molecular experiments have shed considerable light on these and other issues relevant to the chromosomal biology of this interesting protein family.
Highlights
The methyl CpG binding domain (MBD) family Eukaryotic chromosomes are the repositories of the genetic information necessary to direct the synthesis of cellular components
If their binding to chromatin is influenced solely by the interaction of the MBD motif with methylated CpG sequences – the ‘random interaction’ model – one might expect a given methylated locus to be randomly associated with different MBD proteins within a population of cells
These results provide a glimpse into the behavior of MBD proteins on methylated DNA in primary human cells
Summary
Methylation of DNA in mammalian cells serves to demarcate functionally specialized regions of the genome and is strongly associated with transcriptional repression. A highly conserved family of DNA-binding proteins characterized by a common sequence motif is widely believed to convert the information represented by methylation patterns into the appropriate functional state. This family, the MBD family, has been characterized at both the biochemical and genetic levels. Some MBD family members, such as MeCP2, have considerable selectivity for specific sequences. Other family members, such as MBD2, appear to bind with somewhat relaxed specificity to methylated DNA.
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