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.
Yates
Joel A
JA
The Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Menon
Tushar
T
Thompson
Brandi A
BA
Bochar
Daniel A
DA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
C485622:ASH2L protein, human; C523331:CHD8 protein, human; D004268:DNA-Binding Proteins; C520321:HOXA2 protein, human; D006657:Histones; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C470552:RBBP5 protein, human; D014157:Transcription Factors; C502547:WDR5 protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D014212:Tretinoin; D000255:Adenosine Triphosphate; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine