PreprintCited by 306Epigenetics and DNA MethylationGenomics and Chromatin DynamicsCancer-related gene regulation

Sp1 transcription factor binds DNA and activates transcription even when the binding site is CpG methylated

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Höller, M, Westin, G, Jiricny, J, Schaffner, W·1988·Genes & Development

Abstract

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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Research works printed but not linked: 5

  1. Cristy, B.A. and G.A. Scangos. 1986. Control of gene expression by DNA methylation. In Molecular genetics of mammalian cells (ed. G.M. Malacinski), pp. 3-29. Macmillan Publishing Co., New York.
  2. de Villiers, J. and W. Schaffner. 1983. Transcriptional 'en- hancers' from papovaviruses as components of eukaryotic expression vectors. In Techniques in the life sciences, B5. Nucleic Acid Biochemistry. Elsevier, Ireland.
  3. Harrington, M.A., P.A. Jones, M. Imagawa, and M. Karin. 1988. Cytidine methylation does not affect binding of transcrip- tion factor Spl. Proc. Natl. Acad. Sci. 85: 2066-2070.
  4. Parker, J.-H., H.V. Hershey, and M.W. Taylor. 1986. House- keeping genes. In Molecular genetics of mammalian cells (ed. G.M. Malacinski), pp. 79-98. Macmillan Pubhshing Co., New York.
  5. Siebenhst, U. and W. Gilbert. 1980. Contacts between Esche- richia coh RNA polymerse and an early promoter of phage T7. Proc. Natl. Acad. Sci. 77: 122-126.

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Authors
Höller, M., Westin, G., Jiricny, J., & Schaffner, W.
Affiliations
University of Zurich (CH)
Venue
Genes & Development
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
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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