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Gene Review

MBD2  -  methyl-CpG binding domain protein 2

Homo sapiens

Synonyms: DMTase, Demethylase, Methyl-CpG-binding domain protein 2, Methyl-CpG-binding protein MBD2, NY-CO-41
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Disease relevance of MBD2


High impact information on MBD2

  • Importantly, studies in zebrafish and primary mammalian neurons demonstrated a role for SMCX in neuronal survival and dendritic development and a link to the demethylase activity [6].
  • The recently identified histone demethylase lysine-specific demethylase 1 (LSD1) is chemically restricted to demethylation of only mono- and di- but not trimethylated histone H3 lysine 4 (H3K4me3) [6].
  • Sited-directed mutagenesis in conjunction with demethylase activity assays allowed us to propose a molecular model for substrate selection by the JMJD2 histone demethylase family [7].
  • They showed that LSD 1, a nuclear amine oxidase homolog, is a bona fide histone H3 lysine 4 demethylase (Shi et al., 2004) [8].
  • The results thus identify a histone demethylase conserved from S. pombe to human and reveal dynamic regulation of histone methylation by both histone methylases and demethylases [9].

Chemical compound and disease context of MBD2


Biological context of MBD2


Anatomical context of MBD2

  • Our data suggest that HeLa cells, which lack the known methylation-dependent repressor MeCP2, use an alternative pathway involving MBD2 to silence methylated genes [13].
  • However, there was no protein expression for MBD2 and MeCP2 in cancer cell lines and cancer tissues [17].
  • In both male and female fetal gonads expression of genes for MBD2 and MBD4, which may be implicated in chromatin remodeling of methylated genomic DNA sequences, was tightly linked to DNMT expression [18].
  • Slightly reduced expression of MBD2 was detected in HCCs, and the expression of MeCP2 was particularly reduced in HCCs with portal vein involvement [19].
  • No significant changes in MeCP2 or MBD2 expression were found when NB4 cells were differentiated toward granulocytes suggesting that neither differentiation nor cell cycle status were relevant for the reduced expression of these genes in human cancer [4].

Associations of MBD2 with chemical compounds


Physical interactions of MBD2


Regulatory relationships of MBD2


Other interactions of MBD2

  • Expression of MBD2 and MBD4 tagged with green fluorescent protein in mouse cells shows that both proteins colocalize with foci of heavily methylated satellite DNA [14].
  • MBD2 and MBD3 are two proteins that contain methyl-CpG binding domains and have a transcriptional repression function [30].
  • The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex [31].
  • MeCP2, MBD1 and MBD2 can also repress transcription [32].
  • Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells [1].

Analytical, diagnostic and therapeutic context of MBD2


  1. Methyl-CpG-binding domain protein-2 mediates transcriptional repression associated with hypermethylated GSTP1 CpG islands in MCF-7 breast cancer cells. Lin, X., Nelson, W.G. Cancer Res. (2003) [Pubmed]
  2. CpG island promoter methylation and silencing of 14-3-3sigma gene expression in LNCaP and Tramp-C1 prostate cancer cell lines is associated with methyl-CpG-binding protein MBD2. Pulukuri, S.M., Rao, J.S. Oncogene (2006) [Pubmed]
  3. MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers. Bader, S., Walker, M., McQueen, H.A., Sellar, R., Oei, E., Wopereis, S., Zhu, Y., Peter, A., Bird, A.P., Harrison, D.J. Oncogene (2003) [Pubmed]
  4. Loss of expression of HDAC-recruiting methyl-CpG-binding domain proteins in human cancer. Müller-Tidow, C., Kügler, K., Diederichs, S., Klümpen, S., Möller, M., Vogt, U., Metzger, R., Schneider, P.M., Berdel, W.E., Serve, H. Br. J. Cancer (2001) [Pubmed]
  5. Role of MBD2 in gene regulation and tumorigenesis. Berger, J., Bird, A. Biochem. Soc. Trans. (2005) [Pubmed]
  6. The X-Linked Mental Retardation Gene SMCX/JARID1C Defines a Family of Histone H3 Lysine 4 Demethylases. Iwase, S., Lan, F., Bayliss, P., de la Torre-Ubieta, L., Huarte, M., Qi, H.H., Whetstine, J.R., Bonni, A., Roberts, T.M., Shi, Y. Cell (2007) [Pubmed]
  7. Structural insights into histone demethylation by JMJD2 family members. Chen, Z., Zang, J., Whetstine, J., Hong, X., Davrazou, F., Kutateladze, T.G., Simpson, M., Mao, Q., Pan, C.H., Dai, S., Hagman, J., Hansen, K., Shi, Y., Zhang, G. Cell (2006) [Pubmed]
  8. Taking LSD 1 to a new high. Wysocka, J., Milne, T.A., Allis, C.D. Cell (2005) [Pubmed]
  9. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Shi, Y., Lan, F., Matson, C., Mulligan, P., Whetstine, J.R., Cole, P.A., Casero, R.A., Shi, Y. Cell (2004) [Pubmed]
  10. Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins. Tryndyak, V.P., Kovalchuk, O., Pogribny, I.P. Cancer Biol. Ther. (2006) [Pubmed]
  11. Nitrogen metabolism in the facultative methylotroph Arthrobacter P1 grown with various amines or ammonia as nitrogen sources. De Boer, L., Brouwer, J.W., Van Hassel, C.W., Levering, P.R., Dijkhuizen, L. Antonie Van Leeuwenhoek (1989) [Pubmed]
  12. Specific treatment of Chagas disease: current status and new developments. Urbina, J.A. Curr. Opin. Infect. Dis. (2001) [Pubmed]
  13. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Ng, H.H., Zhang, Y., Hendrich, B., Johnson, C.A., Turner, B.M., Erdjument-Bromage, H., Tempst, P., Reinberg, D., Bird, A. Nat. Genet. (1999) [Pubmed]
  14. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Hendrich, B., Bird, A. Mol. Cell. Biol. (1998) [Pubmed]
  15. Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression. Ghoshal, K., Majumder, S., Datta, J., Motiwala, T., Bai, S., Sharma, S.M., Frankel, W., Jacob, S.T. J. Biol. Chem. (2004) [Pubmed]
  16. Involvement of a novel zinc finger protein, MIZF, in transcriptional repression by interacting with a methyl-CpG-binding protein, MBD2. Sekimata, M., Takahashi, A., Murakami-Sekimata, A., Homma, Y. J. Biol. Chem. (2001) [Pubmed]
  17. Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2. Patra, S.K., Patra, A., Zhao, H., Carroll, P., Dahiya, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  18. Sex-specific windows for high mRNA expression of DNA methyltransferases 1 and 3A and methyl-CpG-binding domain proteins 2 and 4 in human fetal gonads. Galetzka, D., Weis, E., Tralau, T., Seidmann, L., Haaf, T. Mol. Reprod. Dev. (2007) [Pubmed]
  19. Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis. Saito, Y., Kanai, Y., Sakamoto, M., Saito, H., Ishii, H., Hirohashi, S. Hepatology (2001) [Pubmed]
  20. MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex. Jiang, C.L., Jin, S.G., Pfeifer, G.P. J. Biol. Chem. (2004) [Pubmed]
  21. Methyl-CpG binding domain protein 2 represses transcription from hypermethylated pi-class glutathione S-transferase gene promoters in hepatocellular carcinoma cells. Bakker, J., Lin, X., Nelson, W.G. J. Biol. Chem. (2002) [Pubmed]
  22. Cytosine methylation represses glutathione S-transferase P1 (GSTP1) gene expression in human prostate cancer cells. Singal, R., van Wert, J., Bashambu, M. Cancer Res. (2001) [Pubmed]
  23. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Zhang, Y., Ng, H.H., Erdjument-Bromage, H., Tempst, P., Bird, A., Reinberg, D. Genes Dev. (1999) [Pubmed]
  24. MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase. Tatematsu, K.I., Yamazaki, T., Ishikawa, F. Genes Cells (2000) [Pubmed]
  25. MIRA-Assisted Microarray Analysis, a New Technology for the Determination of DNA Methylation Patterns, Identifies Frequent Methylation of Homeodomain-Containing Genes in Lung Cancer Cells. Rauch, T., Li, H., Wu, X., Pfeifer, G.P. Cancer Res. (2006) [Pubmed]
  26. Expression of Dnmt1, demethylase, MeCP2 and methylation of tumor-related genes in human gastric cancer. Fang, J.Y., Cheng, Z.H., Chen, Y.X., Lu, R., Yang, L., Zhu, H.Y., Lu, L.G. World J. Gastroenterol. (2004) [Pubmed]
  27. DNA methyltransferase and demethylase in human prostate cancer. Patra, S.K., Patra, A., Zhao, H., Dahiya, R. Mol. Carcinog. (2002) [Pubmed]
  28. Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription. Yu, F., Zingler, N., Schumann, G., Strätling, W.H. Nucleic Acids Res. (2001) [Pubmed]
  29. Inactivation of retinoic acid receptor beta by promoter CpG hypermethylation in gastric cancer. Hayashi, K., Yokozaki, H., Goodison, S., Oue, N., Suzuki, T., Lotan, R., Yasui, W., Tahara, E. Differentiation (2001) [Pubmed]
  30. MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing. Jin, S.G., Jiang, C.L., Rauch, T., Li, H., Pfeifer, G.P. J. Biol. Chem. (2005) [Pubmed]
  31. Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1. Humphrey, G.W., Wang, Y., Russanova, V.R., Hirai, T., Qin, J., Nakatani, Y., Howard, B.H. J. Biol. Chem. (2001) [Pubmed]
  32. Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes. Hendrich, B., Abbott, C., McQueen, H., Chambers, D., Cross, S., Bird, A. Mamm. Genome (1999) [Pubmed]
  33. Methyl-CpG-binding domain 2: a protective role in bladder carcinoma. Zhu, Y., Spitz, M.R., Zhang, H., Grossman, H.B., Frazier, M.L., Wu, X. Cancer (2004) [Pubmed]
  34. DNA methylation status of hMLH1, p16(INK4a), and CDH1 is not associated with mRNA expression levels of DNA methyltransferase and DNA demethylase in gastric carcinomas. Oue, N., Kuraoka, K., Kuniyasu, H., Yokozaki, H., Wakikawa, A., Matsusaki, K., Yasui, W. Oncol. Rep. (2001) [Pubmed]
  35. Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3. Brackertz, M., Boeke, J., Zhang, R., Renkawitz, R. J. Biol. Chem. (2002) [Pubmed]
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