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Review
. 2009 Oct;118(5):549-65.
doi: 10.1007/s00412-009-0221-9. Epub 2009 Jun 9.

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

Ozren Bogdanović  1 , Gert Jan C Veenstra
Affiliations
Review

DNA methylation and methyl-CpG binding proteins: developmental requirements and function

Ozren Bogdanović et al. Chromosoma. 2009 Oct.

Abstract

DNA methylation is a major epigenetic modification in the genomes of higher eukaryotes. In vertebrates, DNA methylation occurs predominantly on the CpG dinucleotide, and approximately 60% to 90% of these dinucleotides are modified. Distinct DNA methylation patterns, which can vary between different tissues and developmental stages, exist on specific loci. Sites of DNA methylation are occupied by various proteins, including methyl-CpG binding domain (MBD) proteins which recruit the enzymatic machinery to establish silent chromatin. Mutations in the MBD family member MeCP2 are the cause of Rett syndrome, a severe neurodevelopmental disorder, whereas other MBDs are known to bind sites of hypermethylation in human cancer cell lines. Here, we review the advances in our understanding of the function of DNA methylation, DNA methyltransferases, and methyl-CpG binding proteins in vertebrate embryonic development. MBDs function in transcriptional repression and long-range interactions in chromatin and also appear to play a role in genomic stability, neural signaling, and transcriptional activation. DNA methylation makes an essential and versatile epigenetic contribution to genome integrity and function.

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Figures

Fig. 1
Fig. 1
Two families of proteins that bind methylated DNA. a Methyl-CpG binding proteins (MBDs): MBD proteins display homology within their MBD domains, while the transcription repression domains (TRD) described for MeCP2, MBD1, and MBD2 are non-homologous. In addition to its MBD domain, MBD1 is able to bind unmethylated DNA via its third CxxC zinc-finger motif. MBD2 features a characteristic stretch of glycine and arginine residues (GR) and has juxtaposed MBD and TRD domains. MBD3 is, due to a mutation in the MBD domain, not able to bind methylated CpGs in mammals. MBD4, a thymine glycosylase, contains a C-terminal glycosylase domain used for excision-based DNA repair. b Kaiso protein family: three members of the Kaiso protein family have been described so far. Kaiso, ZBTB4, and ZBTB38 share a triple zinc-finger domain and a BTB/POZ domain which in case of ZBTB4 contains a 60 amino acid insertion. Furthermore, ZBTB4 and ZBTB38 contain respectively three and seven additional zinc-fingers
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