Abstract
MBD2 and MBD3 are closely related proteins with consensus methyl-CpG binding domains. MBD2 is a transcriptional repressor that specifically binds to methylated DNA and is a component of the MeCP1 protein complex. In contrast, MBD3 fails to bind methylated DNA in murine cells, and is a component of the Mi-2/NuRD corepressor complex. We show by gene targeting that the two proteins are not functionally redundant in mice, as Mbd3(−/−) mice die during early embryogenesis, whereas Mbd2(−/−) mice are viable and fertile. Maternal behavior of Mbd2(−/−) mice is however defective and, at the molecular level, Mbd2(−/−) mice lack a component of MeCP1.Mbd2-mutant cells fail to fully silence transcription from exogenous methylated templates, but inappropriate activation of endogenous imprinted genes or retroviral sequences was not detected. Despite their differences, Mbd3 and Mbd2 interact genetically suggesting a functional relationship. Genetic and biochemical data together favor the view that MBD3 is a key component of the Mi-2/NuRD corepressor complex, whereas MBD2 may be one of several factors that can recruit this complex to DNA.
References
58
Referenced
418
10.1016/S0168-9525(00)02066-7
10.1038/13810
10.1016/0092-8674(89)90431-5
10.1146/annurev.genet.31.1.493
10.1038/17533
10.1016/0092-8674(92)90526-I
10.1016/0168-9525(87)90294-0
10.1016/S0092-8674(00)81532-9
10.1074/jbc.M005929200
10.1016/0092-8674(91)90267-3
10.1002/j.1460-2075.1992.tb05055.x
/ EMBO J. / Repression of genes by DNA methylation depends upon CpG density and promoter strength: Evidence for involvement of a methyl-CpG binding protein. (1992)10.1038/17492
10.1038/85906
10.1093/nar/11.3.647
10.1038/ng0797-256
/ Nat. Genet. / A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins. by Cross (1997)10.1073/pnas.94.19.10243
10.1038/85899
10.1146/annurev.genet.31.1.571
10.1007/s003359901112
10.1128/MCB.18.11.6538
/ Mol. Cell. Biol. / Identification and characterization of a family of mammalian methyl-CpG binding proteins. by Hendrich (1998){'key': '2021111507334062000_15.6.710.21', 'first-page': '55', 'article-title': 'Mammalian methyltransferases and methyl-CpG-binding domains: Proteins involved in DNA methylation.', 'volume': '249', 'year': '2000', 'journal-title': 'Curr. Top. Microbiol. Immunol.'}
/ Curr. Top. Microbiol. Immunol. / Mammalian methyltransferases and methyl-CpG-binding domains: Proteins involved in DNA methylation. (2000)10.1038/45843
{'key': '2021111507334062000_15.6.710.23', 'first-page': '35', 'article-title': 'Promoter-region hypermethylation and gene silencing in human cancer.', 'volume': '249', 'author': 'Herman', 'year': '2000', 'journal-title': 'Curr. Top. Microbiol. Immunol.'}
/ Curr. Top. Microbiol. Immunol. / Promoter-region hypermethylation and gene silencing in human cancer. by Herman (2000)- Hogan B. Beddington R. Constantini F. Lacy E. (1994) Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY), 2nd ed..
10.1038/83730
10.1073/pnas.82.5.1451
10.1038/298623a0
10.1038/561
10.1126/science.282.5395.1897
10.1038/2464
10.1016/0092-8674(92)90610-O
10.1038/366362a0
10.1016/0092-8674(92)90611-F
10.1126/science.284.5412.330
10.1016/0092-8674(89)90430-3
10.1093/nar/21.21.4886
10.1016/S0092-8674(00)81887-5
10.1128/MCB.16.1.414
/ Mol. Cell. Biol. / DNA methylation specifies chromosomal localization of MeCP2. by Nan (1996)10.1038/30764
10.1038/12659
/ Nat. Genet. / MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. by Ng (1999)10.1016/S0092-8674(00)81656-6
10.1073/pnas.97.10.5237
10.1073/pnas.92.14.6592
10.1016/S0960-9822(00)00343-2
10.1101/gad.14.3.313
/ Genes & Dev. / Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos. by Stancheva (2000)10.1038/ng0296-205
10.1046/j.1365-2443.2000.00359.x
10.1016/0092-8674(89)90905-7
10.1038/27699
10.1038/70490
10.1242/dev.127.24.5277
/ Development / The C. elegans Mi-2 chromatin-remodelling proteins function in vulval cell fate determination. by von Zelewsky (2000)10.1016/S0960-9822(98)70328-8
10.1038/12664
/ Nat. Genet. / Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation. by Wade (1999)10.1101/gad.13.1.26
10.1038/2413
10.1016/S1097-2765(00)80299-3
10.1016/S0092-8674(00)81758-4
10.1101/gad.13.15.1924
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 8 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 15, 2021, 10:36 a.m.) |
Indexed | 6 hours, 59 minutes ago (Aug. 30, 2025, 12:33 p.m.) |
Issued | 24 years, 5 months ago (March 15, 2001) |
Published | 24 years, 5 months ago (March 15, 2001) |
Published Online | 24 years, 5 months ago (March 15, 2001) |
Published Print | 24 years, 5 months ago (March 15, 2001) |
@article{Hendrich_2001, title={Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development}, volume={15}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.194101}, DOI={10.1101/gad.194101}, number={6}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Hendrich, Brian and Guy, Jacqueline and Ramsahoye, Bernard and Wilson, Valerie A. and Bird, Adrian}, year={2001}, month=mar, pages={710–723} }