| Structural highlights
Function
[MBD1_HUMAN] Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binding is abolished by the presence of 7-mG that is produced by DNA damage by methylmethanesulfonate (MMS). Acts as transcriptional repressor and plays a role in gene silencing by recruiting AFT7IP, which in turn recruits factors such as the histone methyltransferase SETDB1. Probably forms a complex with SETDB1 and ATF7IP that represses transcription and couples DNA methylation and histone 'Lys-9' trimethylation. Isoform 1 and isoform 2 can also repress transcription from unmethylated promoters.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
CpG methylation in vertebrates is important for gene silencing, alterations in chromatin structure and genomic stability, and differences in the DNA-methylation status are correlated with imprinting phenomena, carcinogenesis and embryonic development. Methylation signals are interpreted by protein factors that contain shared methyl-CpG-binding domains (MBDs). We have determined the solution structure of the MBD of the human methylation-dependent transcriptional repressor MBD1 by multi-dimensional heteronuclear NMR spectroscopy. It folds into an alpha/beta-sandwich structure with characteristic loops. Basic residues conserved in the MBD family are largely confined to one face of this fold and a flexible loop, which together form a large positively charged surface. Site-directed mutagenesis and chemical shift changes upon complexing with a methylated DNA facilitated identification of this surface as the DNA interaction site. In addition to three basic residues, conserved Tyr34 and Asp32 were shown to be important for the DNA binding.
Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1.,Ohki I, Shimotake N, Fujita N, Nakao M, Shirakawa M EMBO J. 1999 Dec 1;18(23):6653-61. PMID:10581239[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cross SH, Meehan RR, Nan X, Bird A. A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins. Nat Genet. 1997 Jul;16(3):256-9. PMID:9207790 doi:http://dx.doi.org/10.1038/ng0797-256
- ↑ Fujita N, Takebayashi S, Okumura K, Kudo S, Chiba T, Saya H, Nakao M. Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein MBD1 isoforms. Mol Cell Biol. 1999 Sep;19(9):6415-26. PMID:10454587
- ↑ Hendrich B, Bird A. Identification and characterization of a family of mammalian methyl-CpG binding proteins. Mol Cell Biol. 1998 Nov;18(11):6538-47. PMID:9774669
- ↑ Ng HH, Jeppesen P, Bird A. Active repression of methylated genes by the chromosomal protein MBD1. Mol Cell Biol. 2000 Feb;20(4):1394-406. PMID:10648624
- ↑ Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M. Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem. 2003 Jun 27;278(26):24132-8. Epub 2003 Apr 23. PMID:12711603 doi:http://dx.doi.org/10.1074/jbc.M302283200
- ↑ Fujita N, Watanabe S, Ichimura T, Ohkuma Y, Chiba T, Saya H, Nakao M. MCAF mediates MBD1-dependent transcriptional repression. Mol Cell Biol. 2003 Apr;23(8):2834-43. PMID:12665582
- ↑ Reese BE, Bachman KE, Baylin SB, Rountree MR. The methyl-CpG binding protein MBD1 interacts with the p150 subunit of chromatin assembly factor 1. Mol Cell Biol. 2003 May;23(9):3226-36. PMID:12697822
- ↑ Ghoshal K, Majumder S, Datta J, Motiwala T, Bai S, Sharma SM, Frankel W, Jacob ST. Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression. J Biol Chem. 2004 Feb 20;279(8):6783-93. Epub 2003 Nov 10. PMID:14610093 doi:http://dx.doi.org/10.1074/jbc.M309393200
- ↑ Sarraf SA, Stancheva I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell. 2004 Aug 27;15(4):595-605. PMID:15327775 doi:http://dx.doi.org/10.1016/j.molcel.2004.06.043
- ↑ Watanabe S, Ichimura T, Fujita N, Tsuruzoe S, Ohki I, Shirakawa M, Kawasuji M, Nakao M. Methylated DNA-binding domain 1 and methylpurine-DNA glycosylase link transcriptional repression and DNA repair in chromatin. Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12859-64. Epub 2003 Oct 10. PMID:14555760 doi:http://dx.doi.org/10.1073/pnas.2131819100
- ↑ Ohki I, Shimotake N, Fujita N, Nakao M, Shirakawa M. Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1. EMBO J. 1999 Dec 1;18(23):6653-61. PMID:10581239 doi:10.1093/emboj/18.23.6653
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