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BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter

Oncogene volume 24, pages 6753–6764 (2005)Cite this article

Abstract

BCL11 genes play crucial roles in lymphopoiesis and have been associated with hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell lymphoma. BCL11 proteins are related C2H2 zinc-finger transcription factors that act as transcriptional repressors. Here, we demonstrate the association of the endogenous BCL11B with the nucleosome remodeling and histone deacetylase (NuRD) complex, one of the major transcriptional corepressor complexes in mammalian cells. BCL11B complexes from T lymphocytes possess trichostatin A-sensitive histone deacetylase activity, confirming the functionality of the complexes. Analysis of the BCL11B–NuRD association demonstrated that BCL11B directly interacted with the metastasis-associated proteins MTA1 and MTA2 through the amino-terminal region. We provide evidence for the functional requirement of MTA1 in transcriptional repression mediated by BCL11B through the following: (1) overexpression of MTA1 enhanced the transcriptional repression mediated by BCL11B, (2) knockdown of MTA1 expression by small interfering RNA inhibited BCL11B transcriptional repression activity and (3) MTA1 was specifically recruited to a BCL11B targeted promoter. Taken together, these data support the hypothesis that the NuRD complex mediates transcriptional repression function of BCL11B.

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Abbreviations

BCL11B:

B-cell chronic lymphocytic leukemia/lymphoma 11B

ChIP:

chromatin immunoprecipitation

COUP-TF:

chicken ovalbumin upstream promoter transcription factor

GST:

glutathione S-transferase

HDAC:

histone deacetylase

NuRD:

nucleosome remodeling and deacetylase

MTA1:

metastasis-associated protein 1

MTA2:

metastasis-associated protein 2

SIRT1:

silent mating type information regulation 2 homolog 1

Sir2:

silent information regulator 2

TSA:

trichostatin A

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Acknowledgements

We acknowledge Dr Paul Wade (Emory University) for antibodies against Mi2β, MTA2 and MBD3. We acknowledge Dr Rakesh Kumar (MD Anderson Cancer Center) for advice with MTA1 antibodies. We thank Drs Danny Reinberg (Robert Wood Johnson Medical School), Bruce Stillman (CSH laboratory), F Ishikawa and Motoki Saito (Tokyo Institute of Technology), Edward Seto (University of South Florida), Yi Zhang (Lineberger Comprehensive Cancer Center, UNC), M-J Tsai (Baylor College), Mark Leid (Oregon State University) and Mark Rauchman (Saint Luis University) for constructs. We thank Mary Carioto, Tehmeena Qamar and Bethsaeda Nieves for technical assistance and Debbie Moran for secretarial assistance. We thank Dr Paul Higgins, Dr John Schwarz and Dr Michelle Lennartz (Albany Medical College) for reading the manuscript and helpful suggestions. This work was supported by National Institute of Health/NIAMS grant K01-AR02194 (to DA).

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Authors and Affiliations

  1. Center for Cell Biology and Cancer Research, Albany Medical College, 47 New Scotland Avenue, MC-165, Albany, 12208, NY, USA

    Valeriu B Cismasiu, Karen Adamo, Jennifer Gecewicz, Javier Duque & Dorina Avram

  2. Center for Functional Genomics, SUNY at Albany, One University Place, Rensselaer, 12144, NY, USA

    Qishan Lin

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  1. Valeriu B Cismasiu
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Correspondence to Dorina Avram.

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Cismasiu, V., Adamo, K., Gecewicz, J. et al. BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter. Oncogene 24, 6753–6764 (2005). https://doi.org/10.1038/sj.onc.1208904

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