Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / chemistry*
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Adenosine Triphosphate / metabolism
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Animals
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Cell Nucleus / metabolism
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Chromatin / chemistry*
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Chromatin / metabolism
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DNA Helicases / metabolism
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DNA-Binding Proteins / metabolism*
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Drosophila Proteins / metabolism
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Drosophila melanogaster
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Gene Expression Regulation*
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HeLa Cells
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Histone-Lysine N-Methyltransferase / metabolism
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Homeodomain Proteins / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins
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Models, Biological
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RNA Interference
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Transcription Factors / metabolism*
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Transcription, Genetic
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beta Catenin / metabolism*
Substances
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CHD8 protein, human
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Chromatin
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DNA-Binding Proteins
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Drosophila Proteins
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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Transcription Factors
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WDR5 protein, human
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beta Catenin
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Adenosine Triphosphate
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Histone-Lysine N-Methyltransferase
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DNA Helicases
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kis protein, Drosophila