1ig4

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Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA

Structural highlights

1ig4 is a 3 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Ligands:5CM
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

In vertebrates, the biological consequences of DNA methylation are often mediated by protein factors containing conserved methyl-CpG binding domains (MBDs). Mutations in the MBD protein MeCP2 cause the neurodevelopmental disease Rett syndrome. We report here the solution structure of the MBD of the human methylation-dependent transcriptional regulator MBD1 bound to methylated DNA. DNA binding causes a loop in MBD1 to fold into a major and novel DNA binding interface. Recognition of the methyl groups and CG sequence at the methylation site is due to five highly conserved residues that form a hydrophobic patch. The structure indicates how MBD may access nucleosomal DNA without encountering steric interference from core histones, and provides a basis to interpret mutations linked to Rett syndrome in MeCP2.

Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA.,Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M Cell. 2001 May 18;105(4):487-97. PMID:11371345[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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Citations
44 reviews cite this structure
Heterochromatin revisited.
Grewal et al. (2007)
43 more
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See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
  8. ↑ 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
  9. ↑ 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
  10. ↑ 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
  11. ↑ Ohki I, Shimotake N, Fujita N, Jee J, Ikegami T, Nakao M, Shirakawa M. Solution structure of the methyl-CpG binding domain of human MBD1 in complex with methylated DNA. Cell. 2001 May 18;105(4):487-97. PMID:11371345

Contents


PDB ID 1ig4

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