The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation.
Open accessAbstract
In mammals and other vertebrates, cytosine methylation in CpG sites is often negatively correlated with gene activity. Because methylation of the promoter region is most crucial for this effect, the simplest hypothesis is that CpG methylation interferes with the binding of specific transcription factors. We have examined this hypothesis with two different transcription factor-binding sites that contain a CpG dinucleotide, namely the cAMP-responsive element (CRE; 5'-TGACGTCA) and the Sp1-binding site (5'-GTGAGGCGGTGAGACT). We have reported previously that CpG methylation of the Sp1-binding site affected neither factor binding nor transcription in HeLa cells, which may be related to the fact that Sp1 is typically associated with promoters of housekeeping genes. In contrast, CREs are often associated with promoters of cell type-specific genes. A synthetic oligonucleotide containing two tandem CREs derived from the gene encoding the human glycoprotein hormone alpha-subunit was cloned upstream of a reporter gene. Transcription of this gene was dependent on the CRE sequences in both PC12 and HeLa cells. Bandshift and methylation interference assays show that similar, if not the same, factor(s) bind to the CRE in both cell lines, even though induction by cAMP was only observed in PC12 cells. CpG methylation of the CRE consensus sequences (TGACGTCA) resulted in loss of specific factor binding, as well as loss of transcriptional activity in vitro and in vivo, in both cell types. This suggests that the inactivity of methylated promoters can, at least in some cases, be explained by their inability to bind specific transcription factors.
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“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 [92]
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Metadata
- Authors
- Iguchi-Ariga, S. M., & Schaffner, W.
- Affiliations
- University of Zurich (CH)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1989-05
- Volume
- 3
- Issue
- 5
- Pages
- 612-619
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2153782423
- Cited by
- 559
- References
- 32
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 11 · 2020: 11 · 2019: 15 · 2018: 12 · 2017: 15 · 2016: 18 · 2015: 14 · 2014: 20 · 2013: 19 · 2012: 20
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (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 › Molecular Biology › Cancer-related gene regulation
- Keywords
- CpG methylation, cAMP response element, Sp1 binding site, transcription factor binding, transcriptional activation, promoter methylation, gene silencing, glycoprotein hormone alpha-subunit, PC12 cells, HeLa cells, methylation interference, cAMP signaling
- MeSH terms
- Cyclic AMP, Base Sequence, Binding Sites, Cells, Cultured, DNA, DNA-Binding Proteins, Enhancer Elements, Genetic, HeLa Cells, Humans, Methylation, Molecular Sequence Data, Promoter Regions, Genetic, Transcription, Genetic, Dinucleoside Phosphates
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