MBD3 explained

Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene.^{[1] [2] [3]}

Function

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). However, unlike the other family members, MBD3 is not capable of binding to methylated DNA but instead binds to hydroxymethylated DNA.^[4] The predicted MBD3 protein shares 71% and 94% identity with MBD2 (isoform 1) and mouse Mbd3. MBD3 is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. MBD3 mediates the association of metastasis-associated protein 2 (MTA2) with the core histone deacetylase complex.^[3]

MBD3 also contains the coiled‐coil domain common to all three MBD3 isoforms.^[5]

Interactions

MBD3 has been shown to interact with:

• AURKA,^[6]
• GATAD2B,^{[7] [8]}
• HDAC1,^{[6] [9] [10]}
• MTA2,^{[6] [9] [10]} and
• MBD2.^{[9] [11]}

References

Further reading

• Shen L, Zhang Y . 5-Hydroxymethylcytosine: generation, fate, and genomic distribution . Current Opinion in Cell Biology . 25 . 3 . 289–96 . June 2013 . 23498661 . 4060438 . 10.1016/j.ceb.2013.02.017 .
• Abbott WM, Mellor A, Edwards Y, Feizi T . Soluble bovine galactose-binding lectin. cDNA cloning reveals the complete amino acid sequence and an antigenic relationship with the major encephalitogenic domain of myelin basic protein . The Biochemical Journal . 259 . 1 . 283–90 . April 1989 . 2470348 . 1138502 . 10.1042/bj2590283.
• Zhang Y, LeRoy G, Seelig HP, Lane WS, Reinberg D . The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities . Cell . 95 . 2 . 279–89 . October 1998 . 9790534 . 10.1016/S0092-8674(00)81758-4 . 18786866 . free .
• Tong JK, Hassig CA, Schnitzler GR, Kingston RE, Schreiber SL . Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex . Nature . 395 . 6705 . 917–21 . October 1998 . 9804427 . 10.1038/27699 . 1998Natur.395..917T . 4355885 .
• Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D . Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation . Genes & Development . 13 . 15 . 1924–35 . August 1999 . 10444591 . 316920 . 10.1101/gad.13.15.1924 .
• Wade PA, Gegonne A, Jones PL, Ballestar E, Aubry F, Wolffe AP . Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation . Nature Genetics . 23 . 1 . 62–6 . September 1999 . 10471500 . 10.1038/12664 . 52868103 .
• Tatematsu KI, Yamazaki T, Ishikawa F . MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex containing DNMT1 at the replication foci in late S phase . Genes to Cells . 5 . 8 . 677–88 . August 2000 . 10947852 . 10.1046/j.1365-2443.2000.00359.x . 25185979 . free .
• Humphrey GW, Wang Y, Russanova VR, Hirai T, Qin J, Nakatani Y, Howard BH . Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1 . The Journal of Biological Chemistry . 276 . 9 . 6817–24 . March 2001 . 11102443 . 10.1074/jbc.M007372200 . free .
• Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM . Sharp, an inducible cofactor that integrates nuclear receptor repression and activation . Genes & Development . 15 . 9 . 1140–51 . May 2001 . 11331609 . 312688 . 10.1101/gad.871201 .
• Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y . Identification and functional characterization of the p66/p68 components of the MeCP1 complex . Molecular and Cellular Biology . 22 . 2 . 536–46 . January 2002 . 11756549 . 139742 . 10.1128/MCB.22.2.536-546.2002 .
• Schlegel J, Güneysu S, Mennel HD . Expression of the genes of methyl-binding domain proteins in human gliomas . Oncology Reports . 9 . 2 . 393–5 . 2002 . 11836615 . 10.3892/or.9.2.393 .
• Saito M, Ishikawa F . The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2 . The Journal of Biological Chemistry . 277 . 38 . 35434–9 . September 2002 . 12124384 . 10.1074/jbc.M203455200 . free .
• Brackertz M, Boeke J, Zhang R, Renkawitz R . Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3 . The Journal of Biological Chemistry . 277 . 43 . 40958–66 . October 2002 . 12183469 . 10.1074/jbc.M207467200 . free .
• Sakai H, Urano T, Ookata K, Kim MH, Hirai Y, Saito M, Nojima Y, Ishikawa F . MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase . The Journal of Biological Chemistry . 277 . 50 . 48714–23 . December 2002 . 12354758 . 10.1074/jbc.M208461200 . free .
• Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA . MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer . Cell . 113 . 2 . 207–19 . April 2003 . 12705869 . 10.1016/S0092-8674(03)00234-4 . 5773916 . free .
• Fujita N, Jaye DL, Geigerman C, Akyildiz A, Mooney MR, Boss JM, Wade PA . MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation . Cell . 119 . 1 . 75–86 . October 2004 . 15454082 . 10.1016/j.cell.2004.09.014 . 17391732 . free .

Notes and References

1. Hendrich B, Bird A . Identification and characterization of a family of mammalian methyl-CpG binding proteins . Molecular and Cellular Biology . 18 . 11 . 6538–47 . November 1998 . 9774669 . 109239 . 10.1128/mcb.18.11.6538.
2. Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A . Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes . Mammalian Genome . 10 . 9 . 906–12 . September 1999 . 10441743 . 10.1007/s003359901112 . 819148 .
3. Web site: Entrez Gene: MBD3 methyl-CpG binding domain protein 3.
4. Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, Weng Z, Rando OJ, Fazzio TG . Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells . Cell . 147 . 7 . 1498–510 . December 2011 . 22196727 . 3252821 . 10.1016/j.cell.2011.11.054 .
5. Hirasaki M, Ueda A, Asaka MN, Uranishi K, Suzuki A, Kohda M, Mizuno Y, Okazaki Y, Nishimoto M, Sharif J, Koseki H, Okuda A . Identification of the Coiled-Coil Domain as an Essential Mbd3 Element for Preserving Lineage Commitment Potential of Embryonic Stem Cells . Stem Cells . 36. 9. May 2018 . 29761578 . 10.1002/stem.2849 . 1355–1367. free .
6. Sakai H, Urano T, Ookata K, Kim MH, Hirai Y, Saito M, Nojima Y, Ishikawa F . MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase . The Journal of Biological Chemistry . 277 . 50 . 48714–23 . December 2002 . 12354758 . 10.1074/jbc.M208461200 . free .
7. Brackertz M, Boeke J, Zhang R, Renkawitz R . Two highly related p66 proteins comprise a new family of potent transcriptional repressors interacting with MBD2 and MBD3 . The Journal of Biological Chemistry . 277 . 43 . 40958–66 . October 2002 . 12183469 . 10.1074/jbc.M207467200 . free .
8. Feng Q, Cao R, Xia L, Erdjument-Bromage H, Tempst P, Zhang Y . Identification and functional characterization of the p66/p68 components of the MeCP1 complex . Molecular and Cellular Biology . 22 . 2 . 536–46 . January 2002 . 11756549 . 139742 . 10.1128/MCB.22.2.536-546.2002 .
9. Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D . Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation . Genes & Development . 13 . 15 . 1924–35 . August 1999 . 10444591 . 316920 . 10.1101/gad.13.15.1924 .
10. Saito M, Ishikawa F . The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2 . The Journal of Biological Chemistry . 277 . 38 . 35434–9 . September 2002 . 12124384 . 10.1074/jbc.M203455200 . free .
11. Jiang CL, Jin SG, Pfeifer GP . MBD3L1 is a transcriptional repressor that interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex . The Journal of Biological Chemistry . 279 . 50 . 52456–64 . December 2004 . 15456747 . 10.1074/jbc.M409149200 . free .