Methyl CpG binding protein

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Function

Methyl CpG binding proteins are called MBD1 to MBD4 and contain a methyl-CpG binding domain (MBD) which binds to methylated DNA[1].

MBD1 is a transcription regulator. It reverts methylated cytosine bases to cytosine.
MBD2 is part of the MeCP1 complex which contains also NuRD. MBD2 recruits histone deacetylases and DNA methyltransferases. MBD2 functions as a scaffold protein promoting repression.
MBD3 binds to hydroxymethylated DNA.
MBD4 has a G:T mispair-specific activity.
Methyl CpG binding protein 2 (MeCP2) is present in mature nerve cells and is involved in turning off several genes. For more details see Methyl CpG Binding Protein 2.

Disease

Mutations in MBD2 are involved in Rett syndrome[2].

Relevance

MBD1 has a role in lung, prostate, pancreatic, colorectal cancers and promyelocytic leukemia. MBD2 has a role in lung, prostate, renal, colorectal cancers. MBD3 has a role in lung, prostate, ovarian cancers and promyelocytic leukemia. MBD4 has a role in gastric, liver and colorectal cancers.

Structural highlights

[3].

3D structures of methyl CpG binding protein

Methyl CpG binding protein 3D structures


Structure of mouse MBD4 glycosylate domain complex with DNA containing mismatch, ethylene glycol and Ni+2 ion (green) (PDB code 4evv).

Drag the structure with the mouse to rotate

ReferencesReferences

  1. Wade PA. Methyl CpG-binding proteins and transcriptional repression. Bioessays. 2001 Dec;23(12):1131-7. PMID:11746232 doi:http://dx.doi.org/10.1002/bies.10008
  2. Van den Veyver IB, Zoghbi HY. Mutations in the gene encoding methyl-CpG-binding protein 2 cause Rett syndrome. Brain Dev. 2001 Dec;23 Suppl 1:S147-51. PMID:11738862
  3. Hashimoto H, Zhang X, Cheng X. Excision of thymine and 5-hydroxymethyluracil by the MBD4 DNA glycosylase domain: structural basis and implications for active DNA demethylation. Nucleic Acids Res. 2012 Jun 27. PMID:22740654 doi:10.1093/nar/gks628

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Michal Harel, Alexander Berchansky