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Histone deacetylase interacts directly with DNA topoisomerase II

Nature Genetics volume 26, pages 349–353 (2000)Cite this article

Abstract

Histone deacetylases (HDACs) modify nucleosomal histones, have a key role in the regulation of gene transcription1,2, and may be involved in cell-cycle regulation, differentiation and human cancer3,4. Purified recombinant human HDAC1 protein was used to screen a cDNA expression library, and one of the clones identified encoded DNA topoisomerase II (Topo II), an enzyme known to have a role in transcriptional regulation and chromatin organization5,6. Coimmunoprecipitation experiments indicate that HDAC1 and HDAC2 are associated with Topo II in vivo under normal physiological conditions. Complexes containing Topo II possess HDAC activities, and complexes containing HDAC1 or HDAC2 possess Topo II activities. HDAC and Topo II modify each other's activity in vitro and in vivo. Our results indicate the existence of a functionally coupled complex between these two enzymes and offer insights into the potential mechanisms of action of both enzymes.

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Figure 1: Cloning of an HDAC-binding protein.
Figure 2: In vivo association of HDAC1/2 with Topo II α/β.
Figure 3: In vitro association of HDAC with Topo II.
Figure 4: Association of HDAC and Topo II enzymatic activities.

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Acknowledgements

We thank I. Hickson for full-length Topo IIβ cDNA; F. Boege for monoclonal anti-Topo IIβ 3H10; Y. Zhang for anti-MTA2 antibody; R. Croxton, R. Jackson, N. Olashaw, C. Shuman, M. Thomas, K. Wright and Y. Yao for discussions and critical reading of the manuscript; and the Moffitt Cancer Center Molecular Biology and Imaging Core Facility for technical support. This work was supported by a grant from the National Institutes of Health (GM58486) to E.S.

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  1. H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, Florida, USA

    Shih-Chang Tsai, Nikola Valkov, Wen-Ming Yang, Jana Gump, Daniel Sullivan & Edward Seto

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Correspondence to Edward Seto.

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Tsai, SC., Valkov, N., Yang, WM. et al. Histone deacetylase interacts directly with DNA topoisomerase II. Nat Genet 26, 349–353 (2000). https://doi.org/10.1038/81671

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