Methylated DNA‐binding Proteins

Esteban Ballestar, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
Manel Esteller, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain

Published online: January 2006

DOI: 10.1038/npg.els.0006157

Abstract

The information encoded by deoxyribonucleic acid methylation is interpreted by a family of proteins that share the methylated CpG‐binding domain. These proteins are associated with histone deacetylase and mediate gene silencing through the modification of chromatin.

Keywords: DNA methylation; gene repression; histone deacetylase; methylated CpG‐binding domain; methyl CpG binding protein 2

Figure 1.

Diagram of the MBD–DNA complex. Coordinates for the MBD1 MBD–methylated DNA complex are available at the Structure Database of the NCBI (see Web Links) with the accession number 1IG4. The figure was drawn with the coordinates and the WebLab ViewerPro 3.2 software. The secondary structure of the MBD is shown (β‐sheet strands and the α‐helix).
Figure 2.

Model showing events that take place in hypermethylated promoters and the factors involved in the establishment of a transcriptionally silenced state. An array of nucleosomes is shown. Acetylated histone tails are protruding lines from octamers, whereas deacetylated histone tails are not shown. Factors involved in DNA‐methylation‐driven repression: the upper half includes CGBP and specific transcription factors that bind exclusively unmethylated DNA and HATs that activate gene expression. The lower half includes HDAC‐associated DNMTs and MBD‐containing repressor complexes that associate to methylated DNA.
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References

Esteller M, Corn PG, Baylin SB and Herman JG (2001) A gene hypermethylation profile of human cancer. Cancer Research 61: 3225–3229.

Hendrich B and Bird A (1998) Identification and characterization of a family of mammalian methyl‐CpG binding proteins. Molecular and Cellular Biology 18: 6538–6547.

Jones PL, Veenstra GJ, Wade PA, et al. (1998) Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription. Nature Genetics 19: 187–191.

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Ng HH, Zhang Y, Hendrich B, et al. (1999) MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nature Genetics 23: 58–61.

Ohki I, Shimotake N, Fujita N, et al. (2001) Solution structure of the methyl‐CpG binding domain of human MBD1 in complex with methylated DNA. Cell 105: 487–497.

Prokhortchouk A, Hendrich B, Jorgensen H, et al. (2001) The p120 catenin partner Kaiso is a DNA methylation‐dependent transcriptional repressor. Genes and Development 15: 1613–1618.

Robertson KD, Ait‐Si‐Ali S, Yokochi T, et al. (2000) DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F‐responsive promoters. Nature Genetics 25: 338–342.

Voo KS, Carlone DL, Jacobsen BM, Flodin A and Skalnik DG (2000) Cloning of a mammalian transcriptional activator that binds unmethylated CpG motifs and shares a CXXC domain with DNA methyltransferase, human trithorax, and methyl‐CpG binding domain protein 1. Molecular and Cellular Biology 20: 2108–2121.

Wade PA, Gegonne A, Jones PL, et al. (1999) Mi‐2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. Nature Genetics 23: 62–66.

Further Reading

Ballestar E and Wolffe AP (2001) Methyl‐CpG‐binding proteins: targeting specific gene repression. European Journal of Biochemistry 268: 1–6.

Bird A (2002) DNA methylation patterns and epigenetic memory. Genes and Development 16: 6–21.

Bird AP and Wolffe AP (1999) Methylation‐induced repression – belts, braces, and chromatin. Cell 99: 451–454.

Esteller M and Herman JG (2002) Cancer as an epigenetic disease: alterations in DNA methylation and chromatin structure. Journal of Pathology 196: 1–7.

Wade PA and Wolffe AP (2001) Methylated DNA‐binding proteins. Nature Structural Biology 8: 575–577.

Wolfe AP (1998) Chromatin: Structure and Function, 3rd edn. New York, NY: Academic Press.

Web Links

Structure Database of the NCBI http://www.ncbi.nlm.nih.gov

Related Sub-Topics:

Transcriptional Regulation | Basic Cell Biology, Protein, RNA and DNA | DNA Structure and Function | Nucleic Acids: Structure, Function, Metabolism | Chromosomes and Chromatin Modifications | Proteins: Structure, Function, Metabolism
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Article Title: Methylated DNA‐binding Proteins
 
How to Cite close
Ballestar, Esteban, and Esteller, Manel(Jan 2006) Methylated DNA‐binding Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006157]