β-Catenin–Histone Deacetylase Interactions Regulate the Transition of LEF1 from a Transcriptional Repressor to an Activator
Open accessAbstract
Recent evidence suggests that certain LEF/TCF family members act as repressors in the absence of Wnt signaling. We show here that repression by LEF1 requires histone deacetylase (HDAC) activity. Further, LEF1 associates in vivo with HDAC1, and transcription of a model LEF1-dependent target gene is modulated by the ratio of HDAC1 to beta-catenin, implying that repression by LEF1 is mediated by promoter-targeted HDAC. Consistent with this hypothesis, under repression conditions the promoter region of a LEF1 target gene is hypoacetylated. By contrast, when the reporter is activated, its promoter becomes hyperacetylated. Coexpression of beta-catenin with LEF1 and HDAC1 results in the formation of a beta-catenin/HDAC1 complex. Surprisingly, the enzymatic activity of HDAC1 associated with beta-catenin is attenuated. Together, these findings imply that activation of LEF1-dependent genes by beta-catenin involves a two-step mechanism. First, HDAC1 is dissociated from LEF1 and its enzymatic activity is attenuated. This first step yields a promoter that is inactive but poised for activation. Second, once HDAC1-dependent repression has been overridden, beta-catenin binds LEF1 and the beta-catenin-LEF1 complex is competent to activate the expression of downstream target genes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inhibition of class I HDACs is associated with activation of Wnt/β-catenin signaling.
“It has been demonstrated that inhibition of class I HDACs is associated with activation of Wnt/β-catenin signaling [42–47].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [47]
The Results report that the HDAC inhibitor TSA stimulated a LEF/TCF-dependent reporter and permitted β-catenin-dependent activation. But TSA alone did not activate the siamois promoter; the paper distinguishes relief of HDAC1-mediated repression from activation, which also required LEF1 and β-catenin. Thus the claim overgeneralizes a conditional reporter finding to activation of Wnt/β-catenin signaling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredβ-catenin interacts with HDAC1 and attenuates its enzymatic activity.
“Finally and importantly, β-catenin interacts with HDAC1 and attenuates its enzymatic activity [47].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
Taunton, J., Hassig, C. A., & Schreiber, S. L. (1996) · Science · doi:10.1126/science.272.5260.408 · Cited by 1,829 · see citing works
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204 · see citing works
Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex
Tong, J. K., Hassig, C. A., Schnitzler, G. R., Kingston, R. E., & Schreiber, S. L. (1998) · Nature · doi:10.1038/27699 · Cited by 692 · see citing works
Histone Deacetylases and SAP18, a Novel Polypeptide, Are Components of a Human Sin3 Complex
Zhang, Y., Iratni, R., Erdjument-Bromage, H., Tempst, P., & Reinberg, D. (1997) · Cell · doi:10.1016/s0092-8674(00)80216-0 · Cited by 578 · see citing works
Histone deacetylases: transcriptional repression with SINers and NuRDs
Ayer, D. E. (1999) · Trends in Cell Biology · doi:10.1016/s0962-8924(99)01536-6 · Cited by 274 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [34]34. Levanon, D., R. E. Goldstein, Y. Bernstein, H. Tang, D. Goldenberg, S. Stifani, Z. Paroush, and Y. Groner. 1998. Transcriptional repression by AML1and LEF-1 is mediated by the TLE/Groucho corepressors. Proc. Natl. Acad. Sci. USA 95: 11590-11595.
- [37]37. Meloni, A. R., E. J. Smith, and J. R. Nevins. 1999. A mechanism for Rb/ p130-mediated transcription repression involving recruitment of the CtBP corepressor. Proc. Natl. Acad. Sci. USA 96: 9574-9579.
Cited by
Sorted by citations
Phiel, C. J., Zhang, F., Huang, E. Y., Guenther, M. G., Lazar, M. A., & Klein, P. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101287200 · Cited by 1,758 · see citing works
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin–TCF interaction
Ye, F., Chen, Y., Hoang, T., Montgomery, R. L., Zhao, X.-H., Bu, H., Hu, T., Taketo, M. M., van Es, J. H., Clevers, H., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2333 · Cited by 559 · see citing works
Deconstructing repression: evolving models of co-repressor action
Perissi, V., Jepsen, K., Glass, C. K., & Rosenfeld, M. G. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2736 · Cited by 532 · see citing works
Structure of Hdac3 Bound to Co-Repressor and Inositol Tetraphosphate
Watson, P. J., Fairall, L., Santos, G. M., & Schwabe, J. W. R. (2012) · Nature · doi:10.1038/nature10728 · Cited by 505 · see citing works
Dorsky, R. I., Sheldahl, L. C., & Moon, R. T. (2002) · Developmental Biology · doi:10.1006/dbio.2001.0515 · Cited by 287 · see citing works
Lu, W., Kawatani, K., Ren, Y., Nambara, T., Jia, L., Jeevaratnam, S., Lee, E., Martinez, P. R., Izhar, T., Wang, N., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01982-0 · Cited by 4 · see citing works
- Authors
- Billin, A. N., Thirlwell, H., & Ayer, D. E.
- Affiliations
- University of Utah (US)
- Corresponding author
- Ayer, Donald E.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-09-01
- Volume
- 20
- Issue
- 18
- Pages
- 6882-6890
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC88764
- OpenAlex
- W2161725170
- Cited by
- 216
- References
- 5
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 8 · 2015: 8 · 2014: 5 · 2013: 9 · 2012: 9
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukemia and Lymphoma Society
- Huntsman Cancer Institute
- National Cancer Institute (3P30 CA42014, P30CA042014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- LEF1, β-catenin, HDAC1, Wnt signaling, transcriptional repression, transcriptional activation, promoter acetylation, protein-protein interaction, corepressors
- MeSH terms
- Cell Line, Cytoskeletal Proteins, DNA-Binding Proteins, HeLa Cells, Histone Deacetylases, Humans, Repressor Proteins, Transcription Factors, Transcription, Genetic, Trans-Activators, beta Catenin, Lymphoid Enhancer-Binding Factor 1, Histone Deacetylase 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
