MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin - PubMed (original) (raw)
MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin
X Nan et al. Cell. 1997.
Free article
Abstract
MeCP2 is an abundant mammalian protein that binds to methylated CpG. We have found that native and recombinant MeCP2 repress transcription in vitro from methylated promoters but do not repress nonmethylated promoters. Repression is nonlinearly dependent on the local density of methylation, becoming significant at the density found in bulk vertebrate genomic DNA. Transient transfection using fusions with the GAL4 DNA binding domain identified a region of MeCP2 that is capable of long-range repression in vivo. Moreover, MeCP2 is able to displace histone H1 from preassembled chromatin that contains methyl-CpG. These properties, together with the abundance of MeCP2 and the high frequency of its 2 bp binding site, suggest a role as a global transcriptional repressor in vertebrate genomes.
Similar articles
- Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex.
Nan X, Ng HH, Johnson CA, Laherty CD, Turner BM, Eisenman RN, Bird A. Nan X, et al. Nature. 1998 May 28;393(6683):386-9. doi: 10.1038/30764. Nature. 1998. PMID: 9620804 - Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylation.
Nguyen CT, Gonzales FA, Jones PA. Nguyen CT, et al. Nucleic Acids Res. 2001 Nov 15;29(22):4598-606. doi: 10.1093/nar/29.22.4598. Nucleic Acids Res. 2001. PMID: 11713309 Free PMC article. - Methyl-CpG-binding protein 2 represses LINE-1 expression and retrotransposition but not Alu transcription.
Yu F, Zingler N, Schumann G, Strätling WH. Yu F, et al. Nucleic Acids Res. 2001 Nov 1;29(21):4493-501. doi: 10.1093/nar/29.21.4493. Nucleic Acids Res. 2001. PMID: 11691937 Free PMC article. - The biological functions of the methyl-CpG-binding protein MeCP2 and its implication in Rett syndrome.
Nan X, Bird A. Nan X, et al. Brain Dev. 2001 Dec;23 Suppl 1:S32-7. doi: 10.1016/s0387-7604(01)00333-3. Brain Dev. 2001. PMID: 11738839 Review. - Binding of the Rett syndrome protein, MeCP2, to methylated and unmethylated DNA and chromatin.
Hansen JC, Ghosh RP, Woodcock CL. Hansen JC, et al. IUBMB Life. 2010 Oct;62(10):732-8. doi: 10.1002/iub.386. IUBMB Life. 2010. PMID: 21031501 Free PMC article. Review.
Cited by
- Rett syndrome.
Gold WA, Percy AK, Neul JL, Cobb SR, Pozzo-Miller L, Issar JK, Ben-Zeev B, Vignoli A, Kaufmann WE. Gold WA, et al. Nat Rev Dis Primers. 2024 Nov 7;10(1):84. doi: 10.1038/s41572-024-00568-0. Nat Rev Dis Primers. 2024. PMID: 39511247 Review. - RettDb: the Rett syndrome omics database to navigate the Rett syndrome genomic landscape.
Cillari N, Neri G, Pisanti N, Milazzo P, Borello U. Cillari N, et al. Database (Oxford). 2024 Oct 16;2024:baae109. doi: 10.1093/database/baae109. Database (Oxford). 2024. PMID: 39414258 Free PMC article. - The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders.
Kantor B, O'Donovan B, Rittiner J, Hodgson D, Lindner N, Guerrero S, Dong W, Zhang A, Chiba-Falek O. Kantor B, et al. Nat Commun. 2024 Aug 23;15(1):7259. doi: 10.1038/s41467-024-50515-6. Nat Commun. 2024. PMID: 39179542 Free PMC article. - Differential dynamics specify MeCP2 function at nucleosomes and methylated DNA.
Chua GNL, Watters JW, Olinares PDB, Begum M, Vostal LE, Luo JA, Chait BT, Liu S. Chua GNL, et al. Nat Struct Mol Biol. 2024 Nov;31(11):1789-1797. doi: 10.1038/s41594-024-01373-9. Epub 2024 Aug 20. Nat Struct Mol Biol. 2024. PMID: 39164525 Free PMC article. - Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.
Kalani L, Kim BH, de Chavez AR, Roemer A, Mikhailov A, Merritt JK, Good KV, Chow RL, Delaney KR, Hendzel MJ, Zhou Z, Neul JL, Vincent JB, Ausió J. Kalani L, et al. Hum Mol Genet. 2024 Nov 5;33(21):1833-1845. doi: 10.1093/hmg/ddae119. Hum Mol Genet. 2024. PMID: 39137370 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases