The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl‐CpG binding protein.
Open accessAbstract
Repression of transcription from densely methylated genes can be mediated by the methyl-CpG binding protein MeCP-1 (Boyes and Bird, 1991). Here we have investigated the effect of methylation on genes with a low density of methyl-CpG. We found that sparse methylation could repress transfected genes completely, but the inhibition was fully overcome by the presence in cis of an SV40 enhancer. Densely methylated genes, however, could not be reactivated by the enhancer. In vitro studies showed that the sparsely methylated genes bound weakly to MeCP-1 and that binding interfered with transcription. In the absence of available MeCP-1, methylation had minimal effects on transcription. From these and other results we propose that sparsely methylated genes form an unstable complex with MeCP-1 which prevents transcription when the promoter is weak. This complex can be disrupted by a strong promoter, thereby allowing the methylated gene to be transcribed.
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“DNA methylation (5-methylcytosine or 5mC) is associated with gene repression (16) and can disrupt the binding of many TFs (17, 18).”
From Hepatocyte Nuclear Factor 4‐Alpha Is Essential for the Active Epigenetic State at Enhancers in Mouse Liver (2019) · cites this paper as [16]
In the citing paper
“Our finding that targeted DNA methylation outside of annotated CGIs can lead to robust memorized gene silencing extends the canonical model of methylation-based gene silencing, which posits that a high density of CpG methylation is a requirement for stable propagation of silencing (Boyes and Bird, 1992).”
From Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing (2021) · cites this paper as Boyes and Bird, 1992
Citations
Cites
CpG-rich islands and the function of DNA methylation
Bird, A. P. (1986) · Nature · doi:10.1038/321209a0 · Cited by 3,777
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DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124
“The degree of repression may be weak or strong depending on the density of methylation (Boyes and Bird 1992; Hsieh 1994).”
BackgroundSelf-citationWeber, M., Hellmann, I., Stadler, M. B., Ramos, L., Pääbo, S., Rebhan, M., & Schübeler, D. (2007) · Nature Genetics · doi:10.1038/ng1990 · Cited by 2,297
Microsatellites in Different Eukaryotic Genomes: Survey and AnalysisPreprint
Tóth, G. J., Gáspári, Z., & Jurka, J. (2000) · Genome Research · doi:10.1101/gr.10.7.967 · Cited by 1,515
“Boyes and Bird (1992) demonstrated that transcriptional repression by DNA methylation depends on CpG density.”
BackgroundMeCP2 Is a Transcriptional Repressor with Abundant Binding Sites in Genomic Chromatin
Nan, X., Campoy, F. J., & Bird, A. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81887-5 · Cited by 1,288
Self-citationLewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., & Bird, A. (1992) · Cell · doi:10.1016/0092-8674(92)90610-o · Cited by 1,371
Self-citation
Metadata
- Authors
- Boyes, J., & Bird, A.
- Affiliations
- Research Institute of Molecular Pathology (AT)
- Venue
- The EMBO Journal
- Published
- 1992-01-01
- Volume
- 11
- Issue
- 1
- Pages
- 327-333
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC556453
- OpenAlex
- W1821654469
- Cited by
- 471
- References
- 0
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 4 · 2022: 12 · 2021: 8 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 12 · 2016: 10 · 2015: 6 · 2014: 14 · 2013: 18 · 2012: 8
- FWCI
- 9.92
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation, transcriptional repression, CpG density, promoter strength, methyl-CpG binding proteins, SV40 enhancer, gene reactivation, transcriptional silencing
- MeSH terms
- Animals, Binding Sites, DNA-Binding Proteins, Gene Expression Regulation, Globins, Methylation, Models, Genetic, Promoter Regions, Genetic, Simian virus 40, Transcription, Genetic, Transfection, DNA Modification Methylases, DNA-Cytosine Methylases, Mice
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