Cited by 471Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

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Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl‐CpG binding protein.

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Boyes, J., Bird, A.·1992·The EMBO Journal

DOI 10.1002/j.1460-2075.1992.tb05055.xPMC PMC556453

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Abstract

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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Authors: Boyes, J., & Bird, A.
Affiliations: Research Institute of Molecular Pathology (AT)
ORCID: Boyes, J.
Bird, A.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1992-01-01
Volume: 11
Issue: 1
Pages: 327-333
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1992.tb05055.x
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl‐CpG binding protein.

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