Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8.
Chromodomain, helicase, DNA-binding protein 8 (CHD8) is an ATP-dependent chromatin remodeling enzyme that has been demonstrated to exist within a large protein complex which includes WDR5, Ash2L, and RbBP5, members of the Mixed Lineage Leukemia (MLL) histone modifying complexes. Here we show that CHD8 relocalizes to the promoter of the ... MLL regulated gene HOXA2 upon gene activation. Depletion of CHD8 enhances HOXA2 expression under activating conditions. Furthermore, depletion of CHD8 results in a loss of the WDR5/Ash2L/RbBP5 subcomplex, and consequently H3K4 trimethylation, at the HOXA2 promoter. These studies suggest that CHD8 alters HOXA2 gene expression and regulates the recruitment of chromatin modifying enzymes.
Mesh Terms:
Adenosine Triphosphate, Blotting, Western, Cell Line, Tumor, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Humans, Lysine, Methylation, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Tretinoin
Adenosine Triphosphate, Blotting, Western, Cell Line, Tumor, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Humans, Lysine, Methylation, Myeloid-Lymphoid Leukemia Protein, Nuclear Proteins, Promoter Regions, Genetic, Protein Binding, RNA Interference, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Tretinoin
FEBS Lett.
Date: Feb. 19, 2010
PubMed ID: 20085832
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