MBD1

Protein-coding gene in the species Homo sapiens
MBD1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1IG4, 1D9N, 4D4W

Identifiers
AliasesMBD1, CXXC3, PCM1, RFT, methyl-CpG binding domain protein 1
External IDsOMIM: 156535 MGI: 1333811 HomoloGene: 8414 GeneCards: MBD1
Gene location (Human)
Chromosome 18 (human)
Chr.Chromosome 18 (human)[1]
Chromosome 18 (human)
Genomic location for MBD1
Genomic location for MBD1
Band18q21.1Start50,266,882 bp[1]
End50,281,774 bp[1]
Gene location (Mouse)
Chromosome 18 (mouse)
Chr.Chromosome 18 (mouse)[2]
Chromosome 18 (mouse)
Genomic location for MBD1
Genomic location for MBD1
Band18 E2|18 50.7 cMStart74,400,676 bp[2]
End74,415,803 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • parotid gland

  • pituitary gland

  • anterior pituitary

  • middle temporal gyrus

  • right lobe of thyroid gland

  • skin of abdomen

  • tibia

  • hair follicle

  • left lobe of thyroid gland

  • left uterine tube
Top expressed in
  • lacrimal gland

  • left lobe of liver

  • left colon

  • thymus

  • parotid gland

  • right lung

  • right lung lobe

  • medullary collecting duct

  • ciliary body

  • epididymis
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • DNA binding
  • double-stranded methylated DNA binding
  • zinc ion binding
  • metal ion binding
  • protein binding
  • methyl-CpG binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • nuclear speck
  • nuclear matrix
  • chromosome
  • nucleus
  • nucleoplasm
Biological process
  • regulation of transcription, DNA-templated
  • transcription by RNA polymerase II
  • transcription, DNA-templated
  • negative regulation of transcription, DNA-templated
  • regulation of transcription by RNA polymerase II
  • negative regulation of transcription by RNA polymerase II
  • DNA methylation-dependent heterochromatin assembly
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

4152

17190

Ensembl

ENSG00000141644

ENSMUSG00000024561

UniProt

Q9UIS9

Q9Z2E2

RefSeq (mRNA)
NM_001204136
NM_001204137
NM_001204138
NM_001204139
NM_001204140

NM_001204141
NM_001204142
NM_001204143
NM_001204151
NM_002384
NM_015844
NM_015845
NM_015846
NM_015847
NM_001323942
NM_001323947
NM_001323949
NM_001323950
NM_001323951
NM_001323952
NM_001323953
NM_001323954

NM_013594
NM_001357421
NM_001357422
NM_001357423

RefSeq (protein)
NP_001191065
NP_001191066
NP_001191067
NP_001191068
NP_001191069

NP_001191070
NP_001191071
NP_001191072
NP_001191080
NP_001310871
NP_001310876
NP_001310878
NP_001310879
NP_001310880
NP_001310881
NP_001310882
NP_001310883
NP_002375
NP_056669
NP_056670
NP_056671
NP_056723

NP_038622
NP_001344350
NP_001344351
NP_001344352
NP_001389818

NP_001389819
NP_001389820
NP_001389821
NP_001389823
NP_001389824

Location (UCSC)Chr 18: 50.27 – 50.28 MbChr 18: 74.4 – 74.42 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Methyl-CpG-binding domain protein 1 is a protein that in humans is encoded by the MBD1 gene.[5][6][7] The protein encoded by MBD1 binds to methylated sequences in DNA, and thereby influences transcription. It binds to a variety of methylated sequences, and appears to mediate repression of gene expression. It has been shown to play a role in chromatin modification through interaction with the histone H3K9 methyltransferase SETDB1. H3K9me3 is a repressive modification.

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). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. Five transcript variants of the MBD1 are generated by alternative splicing resulting in protein isoforms that contain one MBD domain, two to three cysteine-rich (CXXC) domains, and some differences in the COOH terminus. All five transcript variants repress transcription from methylated promoters; in addition, variants with three CXXC domains also repress unmethylated promoter activity. MBD1 and MBD2 map very close to each other on chromosome 18q21.[7]

Interactions

MBD1 has been shown to interact with ATF7IP,[8] CBX5,[9][10] CHAF1A[10] and SUV39H1.[9]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141644 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024561 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Cross SH, Meehan RR, Nan X, Bird A (Jul 1997). "A component of the transcriptional repressor MeCP1 shares a motif with DNA methyltransferase and HRX proteins". Nat Genet. 16 (3): 256–9. doi:10.1038/ng0797-256. PMID 9207790. S2CID 23475072.
  6. ^ Hendrich B, Abbott C, McQueen H, Chambers D, Cross S, Bird A (Sep 1999). "Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes". Mamm Genome. 10 (9): 906–12. doi:10.1007/s003359901112. PMID 10441743. S2CID 819148.
  7. ^ a b "Entrez Gene: MBD1 methyl-CpG binding domain protein 1".
  8. ^ Fujita N, Watanabe S, Ichimura T, Ohkuma Y, Chiba T, Saya H, Nakao M (Apr 2003). "MCAF Mediates MBD1-Dependent Transcriptional Repression". Mol. Cell. Biol. 23 (8): 2834–43. doi:10.1128/MCB.23.8.2834-2843.2003. PMC 152570. PMID 12665582.
  9. ^ a b Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M (Jun 2003). "Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression". J. Biol. Chem. 278 (26): 24132–8. doi:10.1074/jbc.M302283200. PMID 12711603.
  10. ^ a b Reese BE, Bachman KE, Baylin SB, Rountree MR (May 2003). "The Methyl-CpG Binding Protein MBD1 Interacts with the p150 Subunit of Chromatin Assembly Factor 1". Mol. Cell. Biol. 23 (9): 3226–36. doi:10.1128/MCB.23.9.3226-3236.2003. PMC 153189. PMID 12697822.

Further reading

  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Hendrich B, Bird A (1998). "Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins". Mol. Cell. Biol. 18 (11): 6538–47. doi:10.1128/MCB.18.11.6538. PMC 109239. PMID 9774669.
  • Ueba T, Kaspar B, Zhao X, Gage FH (1999). "Repression of human fibroblast growth factor 2 by a novel transcription factor". J. Biol. Chem. 274 (15): 10382–7. doi:10.1074/jbc.274.15.10382. PMID 10187827.
  • Fujita N, Takebayashi S, Okumura K, Kudo S, Chiba T, Saya H, Nakao M (1999). "Methylation-Mediated Transcriptional Silencing in Euchromatin by Methyl-CpG Binding Protein MBD1 Isoforms". Mol. Cell. Biol. 19 (9): 6415–26. doi:10.1128/MCB.19.9.6415. PMC 84611. PMID 10454587.
  • Ohki I, Shimotake N, Fujita N, Nakao M, Shirakawa M (2000). "Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1". EMBO J. 18 (23): 6653–61. doi:10.1093/emboj/18.23.6653. PMC 1171728. PMID 10581239.
  • Ng HH, Jeppesen P, Bird A (2000). "Active Repression of Methylated Genes by the Chromosomal Protein MBD1". Mol. Cell. Biol. 20 (4): 1394–406. doi:10.1128/MCB.20.4.1394-1406.2000. PMC 85293. PMID 10648624.
  • Fujita N, Shimotake N, Ohki I, Chiba T, Saya H, Shirakawa M, Nakao M (2000). "Mechanism of Transcriptional Regulation by Methyl-CpG Binding Protein MBD1". Mol. Cell. Biol. 20 (14): 5107–18. doi:10.1128/MCB.20.14.5107-5118.2000. PMC 85960. PMID 10866667.
  • Saito M, Ishikawa F (2002). "The mCpG-binding domain of human MBD3 does not bind to mCpG but interacts with NuRD/Mi2 components HDAC1 and MTA2". J. Biol. Chem. 277 (38): 35434–9. doi:10.1074/jbc.M203455200. PMID 12124384.
  • Beyer KS, Blasi F, Bacchelli E, Klauck SM, Maestrini E, Poustka A (2002). "Mutation analysis of the coding sequence of the MECP2 gene in infantile autism". Hum. Genet. 111 (4–5): 305–9. doi:10.1007/s00439-002-0786-3. PMID 12384770. S2CID 16236528.
  • Patra SK, Patra A, Zhao H, Carroll P, Dahiya R (2003). "Methyl-CpG-DNA binding proteins in human prostate cancer: expression of CXXC sequence containing MBD1 and repression of MBD2 and MeCP2". Biochem. Biophys. Res. Commun. 302 (4): 759–66. doi:10.1016/S0006-291X(03)00253-5. PMID 12646234.
  • Fujita N, Watanabe S, Ichimura T, Ohkuma Y, Chiba T, Saya H, Nakao M (2003). "MCAF Mediates MBD1-Dependent Transcriptional Repression". Mol. Cell. Biol. 23 (8): 2834–43. doi:10.1128/MCB.23.8.2834-2843.2003. PMC 152570. PMID 12665582.
  • Reese BE, Bachman KE, Baylin SB, Rountree MR (2003). "The Methyl-CpG Binding Protein MBD1 Interacts with the p150 Subunit of Chromatin Assembly Factor 1". Mol. Cell. Biol. 23 (9): 3226–36. doi:10.1128/MCB.23.9.3226-3236.2003. PMC 153189. PMID 12697822.
  • Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M, Chiba T, Nakao M (2003). "Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression". J. Biol. Chem. 278 (26): 24132–8. doi:10.1074/jbc.M302283200. PMID 12711603.
  • Carney RM, Wolpert CM, Ravan SA, Shahbazian M, Ashley-Koch A, Cuccaro ML, Vance JM, Pericak-Vance MA (2003). "Identification of MeCP2 mutations in a series of females with autistic disorder". Pediatr. Neurol. 28 (3): 205–11. doi:10.1016/S0887-8994(02)00624-0. PMID 12770674.
  • Georgel PT, Horowitz-Scherer RA, Adkins N, Woodcock CL, Wade PA, Hansen JC (2003). "Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation". J. Biol. Chem. 278 (34): 32181–8. doi:10.1074/jbc.M305308200. PMID 12788925.
  • Watanabe S, Ichimura T, Fujita N, Tsuruzoe S, Ohki I, Shirakawa M, Kawasuji M, Nakao M (2004). "Methylated DNA-binding domain 1 and methylpurine–DNA glycosylase link transcriptional repression and DNA repair in chromatin". Proc. Natl. Acad. Sci. U.S.A. 100 (22): 12859–64. doi:10.1073/pnas.2131819100. PMC 240709. PMID 14555760.
  • v
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  • 1d9n: SOLUTION STRUCTURE OF THE METHYL-CPG-BINDING DOMAIN OF THE METHYLATION-DEPENDENT TRANSCRIPTIONAL REPRESSOR MBD1/PCM1
    1d9n: SOLUTION STRUCTURE OF THE METHYL-CPG-BINDING DOMAIN OF THE METHYLATION-DEPENDENT TRANSCRIPTIONAL REPRESSOR MBD1/PCM1
  • 1ig4: Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA
    1ig4: Solution Structure of the Methyl-CpG-Binding Domain of Human MBD1 in Complex with Methylated DNA