Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated
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In vertebrates, a negative correlation between gene activity and CpG methylation of DNA, notably in the promoter region, is well established. Therefore, it is conceivable that differential binding of transcription factors to methylated versus unmethylated binding sites is crucial for gene activity. Since the consensus binding site of transcription factor Sp1 contains a central CpG, we have investigated the binding of Sp1 factor to unmethylated and synthetically CpG-methylated DNA. A strong Sp1 binding site was methylated on both strands at two CpG positions, located in the center and at the periphery of the recognition sequence. Our studies show that neither binding in vitro, nor transcription in vivo and in vitro are affected by methylation of the Sp1 binding site. We discuss the possibility that binding of Sp1 factor, which is often associated with promoters of housekeeping genes, prevents CpG methylation.
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DNA methylation regulates BACE1 expression, likely through increased SP1 transcription factor binding to CpG sites in the BACE1 promoter.
“Interestingly, DNA methylation regulates BACE1 expression, likely owing to increased SP1 transcription factor binding to CpG sites on the BACE1 promoter region (15,16).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [15]
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- Authors
- Höller, M., Westin, G., Jiricny, J., & Schaffner, W.
- Affiliations
- University of Zurich (CH)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1988-09
- Volume
- 2
- Issue
- 9
- Pages
- 1127-1135
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2004855923
- Cited by
- 305
- References
- 53
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 3 · 2013: 8 · 2012: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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
- Sp1, CpG methylation, DNA methylation, transcription factor binding, transcriptional activation, promoter, housekeeping genes, transcriptional regulation
- MeSH terms
- Animals, Binding Sites, DNA, DNA-Binding Proteins, HeLa Cells, Humans, Methylation, Protein Binding, Transcription Factors, Transcription, Genetic, Sp1 Transcription Factor
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