CHD8 Is an ATP-Dependent Chromatin Remodeling Factor That Regulates β-Catenin Target Genes
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ATP-dependent chromatin remodeling by the CHD family of proteins plays an important role in the regulation of gene transcription. Here we report that full-length CHD8 interacts directly with beta-catenin and that CHD8 is also recruited specifically to the promoter regions of several beta-catenin-responsive genes. Our results indicate that CHD8 negatively regulates beta-catenin-targeted gene expression, since short hairpin RNA against CHD8 results in the activation of several beta-catenin target genes. This regulation is also conserved through evolution; RNA interference against kismet, the apparent Drosophila ortholog of CHD8, results in a similar activation of beta-catenin target genes. We also report the first demonstration of chromatin remodeling activity for a member of the CHD6-9 family of proteins, suggesting that CHD8 functions in transcription through the ATP-dependent modulation of chromatin structure.
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Evidence from fly and human work indicates that CHD8 negatively regulates β-catenin function, either by direct binding or by recruitment to promoters of β-catenin-responsive genes.
“There is mounting evidence from work in both fly and humans that CHD8 negatively regulates β-catenin (CTNNB1) function, either through direct binding to β-catenin, or by recruitment to promoter regions of β-catenin-responsive genes (Thompson et al., 2008).”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Thompson et al., 2008
CHD8 negatively regulates beta-catenin through direct binding and downregulates beta-catenin-responsive genes by recruiting to their promoters.
“CHD8 negatively regulates beta-catenin via direct binding and, furthermore, downregulates beta-catenin-responsive genes by recruitment to their promoter regions [73].”
From A de novo convergence of autism genetics and molecular neuroscience (2014) · cites this paper as [73]
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- Authors
- Thompson, B. A., Tremblay, V., Lin, G., & Bochar, D. A.
- Affiliations
- University of Michigan (US)
- ORCID
- Lin, Grace
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2008-06-01
- Volume
- 28
- Issue
- 12
- Pages
- 3894-3904
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2423111
- OpenAlex
- W2117456217
- Cited by
- 208
- References
- 84
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 12 · 2021: 15 · 2020: 11 · 2019: 17 · 2018: 14 · 2017: 11 · 2016: 8 · 2015: 14 · 2014: 12 · 2013: 10 · 2012: 12
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan (P30 CA46592, 5 P30 CA46592)
- National Institutes of Health (CA46592)
- National Cancer Institute (5P30 CA 46592, P30CA046592)
- National Institute of General Medical Sciences (T32GM007315)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- 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 › Genomics and Chromatin Dynamics
- Keywords
- CHD8, chromatin remodeling, β-catenin, Wnt signaling, transcriptional regulation, protein-protein interaction, promoter recruitment, Kismet, gene expression inhibition, evolutionarily conserved function
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Nucleus, Chromatin, DNA Helicases, DNA-Binding Proteins, Drosophila melanogaster, Gene Expression Regulation, HeLa Cells, Humans, Models, Biological, Histone-Lysine N-Methyltransferase, Transcription Factors, Transcription, Genetic, Homeodomain Proteins, Drosophila Proteins, RNA Interference, Intracellular Signaling Peptides and Proteins, beta Catenin
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