IPR001739
Methyl-CpG DNA binding
InterPro entry
Short name | Methyl_CpG_DNA-bd |
Overlapping homologous superfamilies | |
domain relationships |
Description
Methylation at CpG dinucleotide, the most common DNA modification in eukaryotes, has been correlated with gene silencing associated with various phenomena such as genomic imprinting, transposon and chromosome X inactivation, differentiation, and cancer. Effects of DNA methylation are mediated through proteins which bind to symmetrically methylated CpGs. Such proteins contain a specific domain of ~70 residues, the methyl-CpG-binding domain (MBD), which is linked to additional domains associated with chromatin, such as the bromodomain, the AT hook motif, the SET domain, or the PHD finger. MBD-containing proteins appear to act as structural proteins, which recruit a variety of histone deacetylase (HDAC) complexes and chromatin remodelling factors, leading to chromatin compaction and, consequently, to transcriptional repression. The MBD of MeCP2, MBD1, MBD2, MBD4 and BAZ2 mediates binding to DNA, in case of MeCP2, MBD1 and MBD2 preferentially to methylated CpG. In case of human MBD3 and SETDB1 the MBD has been shown to mediate protein-protein interactions
[3, 1].
The MBD folds into an α/β-sandwich structure comprising a layer of twisted β-sheet, backed by another layer formed by the α1 helix and a hairpin loop at the C terminus. These layers are both amphipathic, with the α1 helix and the β-sheet lying parallel and the hydrophobic faces tightly packed against each other. The β-sheet is composed of two long inner strands (β2 and β3) sandwiched by two shorter outer strands (β1 and β4)
[2].
References
1.Characterization of Arabidopsis thaliana methyl-CpG-binding domain (MBD) proteins. Zemach A, Grafi G. Plant J. 34, 565-72, (2003). View articlePMID: 12787239
2.Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M. Cell 105, 487-97, (2001). View articlePMID: 11371345
3.Comparative study of methyl-CpG-binding domain proteins. Roloff TC, Ropers HH, Nuber UA. BMC Genomics 4, 1, (2003). View articlePMID: 12529184