Eukaryotic gene expression is developmentally regulated, in part by chromatin remodelling, and its dysregulation has been linked to cancer. CHD5 (chromodomain helicase DNA-binding protein 5) is a tumour suppressor gene (TSG) that maps to a region of consistent deletion on 1p36.31 in neuroblastomas (NBs) and other tumour types. CHD5 encodes a protein with chromatin remodelling, helicase and DNA-binding motifs that is preferentially expressed in neural and testicular tissues. CHD5 is highly homologous to CHD3 and CHD4, which are the core subunits of nucleosome remodelling and deacetylation (NuRD) complexes. To determine if CHD5 forms a similar complex, we performed studies on nuclear extracts from NBLS, SY5Y (both with endogenous CHD5 expression), NLF (CHD5 null) and NLF cells stably transfected with CHD5 cDNA (wild-type and V5–histidine-tagged). Immunoprecipitation (IP) was performed with either CHD5 antibody or antibody to V5/histidine-tagged protein. We identified NuRD components both by GST–FOG1 (Friend Of GATA1) pull-down and by IP. We also performed MS/MS analysis to confirm the presence of CHD5 or other protein components of the NuRD complex, as well as to identify other novel proteins. CHD5 was clearly associated with all canonical NuRD components, including metastasis-associated protein (MTA)1/2, GATA zinc finger domain containing 2A (GATAD2A), histone deacetylase (HDAC)1/2, retinoblastoma-binding protein (RBBP)4/7 and methyl DNA-binding domain protein (MBD)2/3, as determined by Western blotting and MS/MS. Our data suggest CHD5 forms a NuRD complex similar to CHD4. However, CHD5–NuRD may also have unique protein associations that confer functional specificity and may contribute to normal development and to tumour suppression in NB and other cancers.
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Research Article|
May 22 2015
The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex
Venkatadri Kolla;
Venkatadri Kolla
*Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
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Koumudi Naraparaju;
Koumudi Naraparaju
*Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
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Tiangang Zhuang;
Tiangang Zhuang
*Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
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Mayumi Higashi;
Mayumi Higashi
*Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
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Sriharsha Kolla;
Sriharsha Kolla
*Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
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Gerd A. Blobel;
Gerd A. Blobel
†Division of Hematology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
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Garrett M. Brodeur
Garrett M. Brodeur
1
*Division of Oncology, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia 19104, PA, U.S.A.
1To whom correspondence should be addressed (email Brodeur@email.chop.edu).
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Publisher: Portland Press Ltd
Received:
January 08 2015
Revision Received:
March 30 2015
Accepted:
March 31 2015
Accepted Manuscript online:
March 31 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem J (2015) 468 (2): 345–352.
Article history
Received:
January 08 2015
Revision Received:
March 30 2015
Accepted:
March 31 2015
Accepted Manuscript online:
March 31 2015
Citation
Venkatadri Kolla, Koumudi Naraparaju, Tiangang Zhuang, Mayumi Higashi, Sriharsha Kolla, Gerd A. Blobel, Garrett M. Brodeur; The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex. Biochem J 1 June 2015; 468 (2): 345–352. doi: https://doi.org/10.1042/BJ20150030
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