CHD8 is an ATP-dependent chromatin remodeling factor that regulates beta-catenin target genes.
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.
Thompson
Brandi A
BA
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109-0606, USA.
Tremblay
Véronique
V
Lin
Grace
G
Bochar
Daniel A
DA
D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D051176:beta Catenin / Q000378:metabolism*
C523331:CHD8 protein, human; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; C502547:WDR5 protein, human; D051176:beta Catenin; D000255:Adenosine Triphosphate; D011495:Histone-Lysine N-Methyltransferase; D004265:DNA Helicases; C118474:kis protein, Drosophila