Biology:MBD1

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Methyl-CpG-binding domain protein 1 is a protein that in humans is encoded by the MBD1 gene. 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.

Interactions

MBD1 has been shown to interact with ATF7IP, CBX5, CHAF1A and SUV39H1.

Further reading

• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "Identification and Characterization of a Family of Mammalian Methyl-CpG Binding Proteins". Mol. Cell. Biol. 18 (11): 6538–47. 1998. doi:10.1128/MCB.18.11.6538. PMID 9774669. 
• "Repression of human fibroblast growth factor 2 by a novel transcription factor". J. Biol. Chem. 274 (15): 10382–7. 1999. doi:10.1074/jbc.274.15.10382. PMID 10187827. 
• "Methylation-Mediated Transcriptional Silencing in Euchromatin by Methyl-CpG Binding Protein MBD1 Isoforms". Mol. Cell. Biol. 19 (9): 6415–26. 1999. doi:10.1128/MCB.19.9.6415. PMID 10454587. 
• "Solution structure of the methyl-CpG-binding domain of the methylation-dependent transcriptional repressor MBD1". EMBO J. 18 (23): 6653–61. 2000. doi:10.1093/emboj/18.23.6653. PMID 10581239. 
• "Active Repression of Methylated Genes by the Chromosomal Protein MBD1". Mol. Cell. Biol. 20 (4): 1394–406. 2000. doi:10.1128/MCB.20.4.1394-1406.2000. PMID 10648624. 
• "Mechanism of Transcriptional Regulation by Methyl-CpG Binding Protein MBD1". Mol. Cell. Biol. 20 (14): 5107–18. 2000. doi:10.1128/MCB.20.14.5107-5118.2000. PMID 10866667. 
• "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. 2002. doi:10.1074/jbc.M203455200. PMID 12124384. 
• "Mutation analysis of the coding sequence of the MECP2 gene in infantile autism". Hum. Genet. 111 (4–5): 305–9. 2002. doi:10.1007/s00439-002-0786-3. PMID 12384770. 
• "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. 2003. doi:10.1016/S0006-291X(03)00253-5. PMID 12646234. 
• "MCAF Mediates MBD1-Dependent Transcriptional Repression". Mol. Cell. Biol. 23 (8): 2834–43. 2003. doi:10.1128/MCB.23.8.2834-2843.2003. PMID 12665582. 
• "The Methyl-CpG Binding Protein MBD1 Interacts with the p150 Subunit of Chromatin Assembly Factor 1". Mol. Cell. Biol. 23 (9): 3226–36. 2003. doi:10.1128/MCB.23.9.3226-3236.2003. PMID 12697822. 
• "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. 2003. doi:10.1074/jbc.M302283200. PMID 12711603. 
• "Identification of MeCP2 mutations in a series of females with autistic disorder". Pediatr. Neurol. 28 (3): 205–11. 2003. doi:10.1016/S0887-8994(02)00624-0. PMID 12770674. 
• "Chromatin compaction by human MeCP2. Assembly of novel secondary chromatin structures in the absence of DNA methylation". J. Biol. Chem. 278 (34): 32181–8. 2003. doi:10.1074/jbc.M305308200. PMID 12788925. 
• "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. 2004. doi:10.1073/pnas.2131819100. PMID 14555760.