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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“Although, hypermethylation of CpG islands is also found in the 30 end of some genes, the density of DNA methylation in promoter or first exon regions correlates inversely with the level of gene transcription.(34) DNA hypermethylation, particularly in the GC-rich promoter region, results in transcription repression tha…”
Background
Hypermethylation of the 5′ CpG island of the gene encoding the serine protease Testisin promotes its loss in testicular tumorigenesis
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“Mechanisms of silencing of gene transcription by DNA methylation occur either through methylation of specific CpG dinucleotides contained within the binding sites for transcription factors (Tate and Bird, 1993) or through methylation of a region of CpG dinucleotides resulting in binding of methyl CpG proteins to the D…”
Background
Non-viral therapeutic approaches to ocular diseases: An overview and future directions
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Acetylation and MAPK phosphorylation cooperate to regulate the degradation of active GATA‐1
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“…1 h at room temperature except anti-ubiquitin and anti-acetyl-GATA-1 antibodies, which were incubated overnight at 41C. RNase protection, S1 mapping and luciferase assay The RNase protection assay was as described (Boyes and Bird, 1992); S1 mapping and probes are as described (Cairns et al, 2003).”
MethodSelf-citation
CpG Island Promoter Region Methylation Patterns of the Inactive-X-Chromosome Hypoxanthine Phosphoribosyltransferase ( Hprt) Gene
Park, J.-G., & Chapman, V. M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.7975-7983.1994 · Cited by 43
“Recent studies have shown that the methyl-CpGbinding protein (MeCP-1) (30) is an indirect inhibitor of transcription from many methylated promoters, including the PGKJ promoter (8, 9).”
Background
DNA hypomethylation and activation of germline-specific genes in cancer.
Smet, C. D., & Loriot, A. (2013) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4419-9967-2_7 · Cited by 50
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Background
Expression of Tumor Suppressor Gene p16INK4 Products in Primary Gastric Cancer
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Binding of Histone H1 to DNA Is Indifferent to Methylation at CpG Sequences
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Self-citation
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BackgroundMethod
Methylation at CpG Sequences Does Not Influence Histone H1 Binding to a Nucleosome Including a Xenopus borealis 5 S rRNA Gene
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Base Excision Repair Facilitates a Functional Relationship Between Guanine Oxidation and Histone Demethylation
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“Methylation of cytosine to 5mC at the CpG sites is an important step in epigenetic transcriptional regulation related to transcriptional repression, X-chromosome inactivation, imprinting, and suppression of parasitic sequences (13,60,83).”
Noninfectious Gene Transfer and Expression Systems for Cancer Gene Therapy
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Methylation status of immunoglobulin x e segments correlates with their recombination potential
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Methylation of Single Sites within the Herpes Simplex Virus tk Coding Region and the Simian Virus 40 T-Antigen Intron Causes Gene Inactivation
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Background
Epigenetic signatures of attachment insecurity and childhood adversity provide evidence for role transition in the pathogenesis of perinatal depression
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Background
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Background

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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