CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2

Comb, Michael; Goodman, Howard M.

doi:10.1093/nar/18.13.3975

Cited by 422Epigenetics and DNA MethylationGenomics and Chromatin DynamicsCancer-related gene regulation

CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2

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Comb, Michael, Goodman, Howard M.·1990·Nucleic Acids Research

DOI 10.1093/nar/18.13.3975PMC PMC331101

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Abstract

DNA methylation at HpaII (CmCGG) sites inhibits expression of a human proenkephalin-CAT fusion gene when it is transiently expressed in CV-1 cells or stably expressed in C6-glioma cells. The inhibitory effects of HpaII methylation have been mapped to a site within the human proenkephalin promoter located at position -72 relative to the start site of transcription. This region spans a cAMP and phorbol ester inducible enhancer and methylation at this position inhibits both basal transcription and transcription induced by either cAMP or TPA. The HpaII site is located within an element which binds the transcription factor AP-2. In vitro methylation at this HpaII site inhibits the binding of AP-2. These results suggest that CpG methylation inhibits proenkephalin gene expression by directly interfering with the binding of a positively acting transcription factor previously shown to be essential for maximal basal, cAMP, and TPA inducible transcription.

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Manipulation of the methylation status of DNA sequences results in differential binding of transcription factors, including E2F, AP2α, MYC and MYN.
“The manipulation of the methylation status of DNA sequences has been shown (mostly in in vitro studies) to result in the differential binding of TFs, including E2F, AP2α, MYC and MYN88–95.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [89]

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Authors: Comb, M., & Goodman, H. M.
Affiliations: Harvard University (US)
Corresponding author: Comb, Michael
Venue: Nucleic Acids Research
Publisher: Oxford University Press (OUP)
Published: 1990
Volume: 18
Issue: 13
Pages: 3975-3982
ISSN: 0305-1048 (ISSN-L)
1362-4962
DOI: 10.1093/nar/18.13.3975
PMC: PMC331101
OpenAlex: W1978172569
Cited by: 422
References: 40
Citations by year: 2026: 2 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 12 · 2017: 7 · 2016: 11 · 2015: 18 · 2014: 22 · 2013: 16 · 2012: 32
FWCI: 4.42
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Nucleic Acids Research (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01da005706-10)
National Institute on Drug Abuse (R01-DA05706-01)
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 › Molecular Biology › Cancer-related gene regulation
Keywords: CpG methylation, DNA methylation, proenkephalin, gene expression regulation, AP2 transcription factor, promoter, enhancers, phorbol ester, transcriptional repression, HpaII restriction sites, C6 glioma cells
MeSH terms: Base Sequence, Cloning, Molecular, Cytosine, DNA, DNA-Binding Proteins, Enkephalins, Gene Expression Regulation, Humans, Methylation, Molecular Sequence Data, Promoter Regions, Genetic, Protein Precursors, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Restriction Mapping, Dinucleoside Phosphates, Deoxyribonucleases, Type II Site-Specific, Deoxyribonuclease HpaII, 5-Methylcytosine, Transcription Factor AP-2

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CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2

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