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

Edited by Ivan Sadowski

Received 12 November 2009; received in revised form 23 December 2009; accepted 7 January 2010. published online 18 January 2010.

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.

Structured summary

MINT-7542810: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0915) with RbBP5 (uniprotkb:Q15291) by anti tag coimmunoprecipitation (MI:0007)

MINT-7542794: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0915) with WDR5 (uniprotkb:P61964) by anti tag coimmunoprecipitation (MI:0007)

MINT-7542820: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0915) with ASH2L (uniprotkb:Q9UBL3) by anti tag coimmunoprecipitation (MI:0007)

MINT-7542769: CHD8 (uniprotkb:Q9HCK8) physically interacts (MI:0914) with RbBP5 (uniprotkb:Q15291), ASH2L (uniprotkb:Q9UBL3) and WDR5 (uniprotkb:P61964) by anti tag coimmunoprecipitation (MI:0007)

Keywords: Chromodomain, helicase, DNA-binding protein 8 (CHD8), HOX gene regulation, ATP-dependent chromatin remodeling, WDR5

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

Corresponding author. Address: The University of Michigan Medical School, 3301E MSRB III, 1150W. Medical Center Drive, Ann Arbor, MI 48109, USA. Fax: +1 734 763 7799.

1 Equal contribution.

2 Present address: Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.

PII: S0014-5793(10)00041-4

doi:10.1016/j.febslet.2010.01.022

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