Cyclic AMP Response Element-Binding Protein (CREB) and CAAT/Enhancer-Binding Protein β (C/EBPβ) Bind Chimeric DNA Sites with High Affinity
Abstract
Basic region leucine zipper (bZIP) proteins are transcription factors that interact selectively with duplex DNA to regulate gene expression. Specifically, the cAMP response element-binding protein (CREB) interacts with the cAMP response element (CRE) DNA site with high affinity, while it binds the CAAT/enhancer-binding protein (CEBP) DNA site with low affinity. Despite the selectivity of CREB for the CRE site, CREB-dependent transcription is observed via chimeric DNA sites with similarities to both CRE and CEBP sites. Because CRE/CEBP and CEBP/CRE chimeric DNA are relevant for transcription regulation but have not been rigorously characterized, quantitative electrophoretic mobility shift assays were used to characterize the binding affinity and specificity of CREB to the sites. In addition to CREB, C/EBPbeta was tested because chimeric DNA was shown to stabilize CREB-C/EBPbeta heterodimerization. Despite previous work, no CREB-C/EBPbeta heterodimer was observed in the presence of chimeric DNA; only CREB and C/EBPbeta homodimers were seen. The CREB homodimer bound to the chimeric sites with high affinity, demonstrating that the presence of one CRE half-site is sufficient for high-affinity interaction. A comparison of CREB and C/EBPbeta homodimers indicated that they bind the chimeric sites with similar, high affinity. Whereas the CRE and CEBP sites preferentially interact with CREB and C/EBPbeta, respectively, the chimeric sites bind CREB and C/EBPbeta competitively. Because D…
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The reduced abundance of two well-characterized CREB targets TrkB and cFos provides further confirmation that CREB-mediated transcription is reduced in rTg4510 mice.
“The reduced abundance of two well-characterized CREB targets TrkB and cFos (52,53) provide further confirmation that CREBmediated transcription is reduced in rTg4510 mice (Supple- mentary Material, Fig. S3).”
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Ljungberg, M. C., Ali, Y. O., Zhu, J., Wu, C.-S., Oka, K., Zhai, R. G., & Lu, H.-C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr492 · Cited by 107 · see citing works
- Authors
- Flammer, J. R., Popova, K. N., & Pflum, M. K. H.
- Affiliations
- Wayne State University (US)
- ORCID
- Pflum, Mary Kay H.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-07-13
- Volume
- 45
- Issue
- 31
- Pages
- 9615-9623
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2057037301
- Cited by
- 18
- References
- 0
- Citations by year
- 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2013: 1
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Keywords
- CREB, C/EBPβ, cAMP response element, bZIP transcription factors, DNA binding affinity, DNA binding specificity, protein homodimerization, protein heterodimerization, transcriptional regulation
- MeSH terms
- Animals, Base Sequence, Binding Sites, Binding, Competitive, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Transcription, Genetic, Cyclic AMP Response Element-Binding Protein, CCAAT-Enhancer-Binding Protein-beta, Electrophoretic Mobility Shift Assay, Rats
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