Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8

Joel A Yates; Tushar Menon; Brandi A Thompson; Daniel A Bochar

doi:10.1016/j.febslet.2010.01.022

Regulation of HOXA2 gene expression by the ATP-dependent chromatin remodeling enzyme CHD8

FEBS Lett. 2010 Feb 19;584(4):689-93. doi: 10.1016/j.febslet.2010.01.022. Epub 2010 Jan 17.

Authors

Joel A Yates¹, Tushar Menon, Brandi A Thompson, Daniel A Bochar

Affiliation

¹ The Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.

PMID: 20085832
DOI: 10.1016/j.febslet.2010.01.022

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism*
Blotting, Western
Cell Line, Tumor
Chromatin Assembly and Disassembly
Chromatin Immunoprecipitation
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Gene Expression Regulation, Neoplastic / drug effects
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / metabolism
Histones / metabolism
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Intracellular Signaling Peptides and Proteins
Lysine / metabolism
Methylation
Myeloid-Lymphoid Leukemia Protein / genetics
Myeloid-Lymphoid Leukemia Protein / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Promoter Regions, Genetic / genetics
Protein Binding
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics
Transcription Factors / metabolism*
Tretinoin / pharmacology

Substances

ASH2L protein, human
CHD8 protein, human
DNA-Binding Proteins
HOXA2 protein, human
Histones
Homeodomain Proteins
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
RBBP5 protein, human
Transcription Factors
WDR5 protein, human
Myeloid-Lymphoid Leukemia Protein
Tretinoin
Adenosine Triphosphate
Histone-Lysine N-Methyltransferase
Lysine